\r\n\tVarious disciplines characterize the constituent components comprising mechatronics, which include physical systems modeling, sensors and actuators, signals and systems, computers and logic systems, and software and data acquisition.
\r\n\tMany new MEMS and Nanotechnology applications will emerge, expanding beyond that which is currently identified or known. Here are a few applications of current interest: new phenomena are addressed nowadays in science and technology.
\r\n\tIn this book, we will deal with physical systems modeling., discuss the physical phenomena involved, the adequate methodology to deal with them, and report a selection of papers recently published for possible applications for MEMS and Nanotechnology.
\r\n\r\n\tIn summary, Nano- and micro-electromechanical systems (NEMS/MEMS) are useful for applications ranging from: The design of MEMS accelerometers, gyroscopes, electrostatic actuators, and microresonators; Interfacial engineering for NEMS/MEMS; Biosensors, magnetic biochips, in vitro diagnostics, cell sorting, magnetic nanoparticles, spin electronic materials and sensors, magnetic inductive heads, and magnetic integrated inductors and transformer’s; Flexible substrates for electronics, sensors, and energy conversion platforms; Nanofabrication and nanopatterning technologies, including self-assembly for device fabrication.
\r\n\t
Industry 4.0 has both expanded the possibilities of digital transformation and increased its importance to manufacturing, with an emphasis on globalization, international trade, and foreign direct investments. Industry 4.0 combines and connects digital and physical technologies including artificial intelligence, the Internet of Things, additive manufacturing, robotics, cloud computing, and others to drive more flexible, responsive, and interconnected enterprises capable of making more informed decisions [1]. The infusion of digital technologies in the value chain processes of research and development, design, production, marketing, distribution, and customer services will drive efficiency in production, thereby increasing the ambits of international trade.
Developed in Germany, currently, Industry 4.0 has become the most discussed issue in the industrial arena in the world. Both managers and policymakers from developed, emerging, and developing countries are debating this issue about how they can participate in this fourth industrial revolution as well as save them from the fallout of this advancement. The issue is still evolving, and experts from all spheres of industry and markets are debating on it. The objective of this chapter is to participate in this debate and explore how Industry 4.0 will evolve in the coming years and how it might affect international trade and the global value chain. We will take an in-depth look into what exactly is Industry 4.0 in our globalized context, what it brings to the table when it comes to international businesses and how international organizations can benefit from Industry 4.0 in their globalization strategies? As a matter of fact, Industry 4.0 outperforms the previous industrial revolutions we have gone through during the past centuries. The fourth industrial revolution is the result of the combination between the real and the virtual world, in which deep learning encourages and challenges human capacities and frontiers, particularly, with the increase of cyber-physical systems. Indeed, the new industrial revolution which develops deep learning is not limited to the use of automation systems based on machine learning, but autonomous ones that do not systematically depend on human beings and which can learn and act by themselves. Industry 4.0 refers to many concepts such as artificial intelligence, smart technologies, smart factories, smart automation, or smart management like the implementation of enterprise resource planning and automation of robotized processes. The global business environment has already started to enhance efficiency with futuristic and high-value-added technologies, from which we are not able to see the frontier clearly for now.
Firstly, we will undertake a brief literature review to explain how we structured our work. We will then be having a great detailed analysis of Industry 4.0 and its main components and how it is changing the way corporations do business in an increasingly connected world. Parallelly, we will explore the opportunities that the fourth industrial revolution brings as well as the challenges which emerged from this new revolution in order to counterbalance and give a realistic view of the latter. Finally, we will illustrate the major strategies that can enable the organization to avail opportunities emanated from Industry 4.0.
Industry 4.0 contributes to the virtualization of a physical production environment that facilitates connectivity and interaction between the machines as well as man and machines in real-time. The automation and connectivity as well as machine learning facilitate the inter-connectivity and improve the production process and bring several benefits to the organization. Some of them are presented in the following sections.
Industry 4.0 is a generator of efficiency. Indeed, the great use of technologies within the different steps in the supply chain helps with optimizing the latter. It is, therefore, cost-effective, time-effective and it globally enhances productivity as well as flexibility and quality of outputs, which also raises the overall reliability of the firm and so the value of the company and its competitiveness. Industry 4.0 is not only about using high technology machines to produce more rapidly. There is indeed much more to that. Industry 4.0 can contribute to streamlining the value chain thanks to its transformation of every aspect of the production process from the logistics, passing through the managerial issues, to the networks, and more generally, the whole structure of firms in the network.
First of all, firms can benefit from
Data is the basis of all the improvements around artificial intelligence and the comprehension of the opportunities that can be taken in the organizations. Used correctly, data and communication tools can help firms to better respond to customers’ demands and allow a better accuracy of forecasts too. Data within the industry can help to see what should be improved in terms of production methods to gain efficiency. In that sense, they can also more easily identify bottleneck products which would result in better opportunity costs. Firms can also benefit from greater management and control thanks to adapted software within the firm. Data can be used to analyze production time and costs, as well as comparisons of portfolios of suppliers and materials to get the best of their interest. It allows a rapid reaction to changes and errors. It also allows a quick adaptation when it comes to stock levels, wherever it is from the production or the purchasing teams’ perspectives. Finally, data is the base of artificial intelligence. Thanks to machine learning, data is used to learn from mistakes and successes, which is crucial to be exponentially improving.
Thanks to data, programs are elaborated to improve the business networks such as suppliers with industries or with clients, or from clients to employees when they make a requirement for a change in the process of making an order. The communication is smoother, quicker, and easier to take action. Technologies also allow better safety of work conditions. The efficiency of new technologies allows companies to be more sustainable thanks to smart production facilities, which allows a better allocation of resources and vertical networking of smart production systems. The vertical networking of smart production systems can be defined as
The most blatant of the effects of efficiency in this modern revolution is customer satisfaction. Indeed, thanks to the advanced technologies, customers demand is well –
Customization is an important issue in the global manufacturing industry, and its relevance is expected to even increase in the future. Customers want to customize the design of their products and by influencing the development and production processes at an early or even late stage. This tendency creates the need for manufacturing companies to move from the objective of better products for their customers to the objective of an individualized understanding of customer needs and specialized, industry-specific solutions [5]. That is to say, a major shift from an economy of scale to an economy of customization regardless of the location of production sites in the global value chain.
This ongoing change of customers’ needs results in more and more system complexity in system design as well as in assembly. Furthermore, commissioning can only be partially compensated by manufacturers’ standardization and modularization efforts. Nevertheless,
Assembly line production systems will also be affected by an increase in flexibility in production. Bortolini et al. [8] state that products produced in assembly lines will not only be able to be personalized but that late customization (i.e., after the order has been placed) will also be possible because real-time information on the status of the production process will be available. This means that customers will not only be involved in the definition and design of the product and its specifications, as is the case with mass customization products but will also be launched once in a late customization mode [9].
In contrast, mass-customized production facilities typically produce large volumes of products that share a common core but may be customized to a certain degree [9], creating production process sections with repetitive larger lots (e.g., automotive press shop) and sections of high product variance (e.g., final automotive assembly). The customers of mass-customized production factories typically customize their products based on a predefined set of configuration options, which can be integrated into a common modular architecture. Mass-customized production type factories are typical in the automotive industry, automotive Tier-1 suppliers, and, to some extent, in the truck, bus, agricultural, and construction equipment sectors. Industrial equipment manufacturers – where factories simultaneously have large production volumes and accommodate an ever-increasing number of variants – run mass- customized production type factories as well.
Therefore, the strategy of providing differentiated products leads to a paradigm change in manufacturing planning, posing new challenges for industrial activities. To satisfy the new kind of markets, industries had to adopt agile models, exploiting the competitive advantages of each organization [10]. These manufacturing models intend to face the uncertainty of the market by increasing the response capability of the organization in order to satisfy the customers with similar costs to mass-production industries [11]. Handling the production of large amounts of customized products presents a tough challenge since product differentiation hampers scale economies.
However, managing the production of personalized or customized goods will be quite demanding, given their different requirements. Finally, when late customization of the customer is possible to be accepted and when it is not, it depends on the production sequence in execution, and when it is possible to apply to re-sequence to incorporate the late customizations. Moreover, the advantages of late customization processes can be achieved only if the system is autonomous and can keep running the fabrication process. The customer needs real-time information about the evolution of the production of its personalized product [12]. And, as Kietzmann et al. [13] comment in the context of additive manufacturing,
Before Industry 4.0, companies used traditional data sources such as production records, internal accounts, and market research reports with a limited range for their decision-making process. The way of data sourcing is changing. Data is more and more generated from sources like sensor-generated data from smart products and data from search engines and social media sites. This technological shift offers multinational compagnies (MNC) the opportunity to access new worldwide business-relevant information. Additionally, technical progression regarding computing power and data storage costs is taking place. This results in the development of big data analytics [14, 15, 16].
To understand the innovational power of big data analytics, it is important to understand the changed concept about time in comparison to data analytics before Industry 4.0. Big data analytics is looking into the future and tries to generate existing and new data sources. The traditional role of information technology has been more backward-looking and concerned with monitoring processes and notifying management of anomalies. Firms that have adopted big data analytics report improvements in productivity and financial performance. For example, analysis of big data can enable managers to identify defects, faults, and shortcomings in the production process at an early stage, optimize automation processes and carry out trend analyses, use resources more efficiently and carry out predictive maintenance [17].
The potential implications of big data analytics for international business are several. In particular, firms will be able to monitor emerging trends and opportunities in overseas markets without the need to make substantial resource commitments in those local marketing affiliates, and they will be able to optimize more effectively their supply, production, and distribution activities around the world [18]. But there are two major drawbacks. The first is that the availability of good-quality big data may well be a source of value for firms, but successful firms will require a range of technical and governance capabilities to analyze and operationalize that data so as to realize the potential benefits [19, 20]. The second is that individuals’ privacy will be under threat from widespread big data applications. Like Facebook knows what we like, Google knows what we browse, and Twitter knows what is on our mind [21].
New data protection laws and/or stronger industry self-regulation will need to be formulated to safeguard the privacy of individuals and companies, and to put limits on what data can be accessed, stored, and transmitted both nationally and across borders [22]; Rose et al. [23]. It has to be discussed who will have legal title over what, and who will bear legal responsibility for, products that involve consumer-generated intellectual property [24] and how will these issues be handled in cross-border settings? Some form of (transnational) governance regime will be necessary to regulate this dilemma between the benefits of big data analytics described earlier and data privacy. Finally, this may influence or even determine the abilities of firms to maximize the commercial potential of big data analytics [25, 26].
The optimization of production and logistics processes allowed by Industry 4.0 could have a major impact on the management of the environmental crisis. Indeed, the processes of Industry 4.0 that allow energy savings and waste reductions to cut costs for firms would be equally beneficial for the preservation of natural resources and biodiversity. The Sustainable Development Goals established by the United Nations include the improvement of energy efficiency and better management of waste. Therefore, the improvements brought by Industry 4.0 would be in adequation with government environmental policies and regulations, which will most probably become much stricter in the coming decades.
Industry 4.0 allows improved production management thanks to the production monitoring capabilities of Industry 4.0. Constant monitoring of production efficiency and intelligent quality control offer great opportunities in terms of production efficiency, waste reduction, and improved reliability. Consequently, firms would have a better energy efficiency [27]. Industry 4.0 allows firms to make informed decisions based on the data-mining possibilities brought by sensors and AI. Relevant statistics on production efficiency, product life cycle, and energy consumption will be available to the firms [28]. Industry 4.0 will also connect the consumer with its energy consumption thanks to the sharing of statistics made possible by smart data communication technologies [29]. Energy consumers will be informed on their consumption, and this will promote self-responsibilities.
However, these improvements could easily be counterbalanced by the fact that Industry 4.0 requires the collection and storing of massive quantities of data in data centers, which significantly contribute to global warming. But this is not a fatality, and firms should not be stopped by this challenge, as innovative solutions allow the heat produced by data centers to be reused as a heating source. This strategy is especially used in Nordic countries such as Finland or Sweden.
Research on Industry 4.0 is numerous and rapidly evolving. Many types of research have addressed the evolution of the Industry 4.0 (I4.0) phenomenon and its contribution to international business activities. Especially the major drivers of I4.0 that underlines its involvement to enhance current business practices by streamlining both the production and supply chain networks [30, 31]. Those developments in Industry 4.0 have huge implications on the way the current business activities both at home as well as across the globe (i.e., international trade) are being conducted. Mamad [2] has addressed how Industry 4.0 works and has made a broad illustration of the subject in detail through an exhaustive literature review. Deloitte [3] provided an overview of the beneficial application of Industry 4.0 to enhance organizational processes. McKinsey’s [6] study focused on customization and explained how Industry 4.0 has reshaped the manufacturing industry to fit customer demand and how companies can reap profit from these upcoming innovations by showing application opportunities. UNIDO [32] report has presented an impact analysis and showed how Industry 4.0 could contribute to environmental sustainability. Jayashree et al. [33] showed how Industry 4.0 could contribute to developing dynamic capabilities and realizing triple bottom line (TBL) sustainability. Bibby et al. [34] give some tools to assess the current level of Industry 4.0 maturity of businesses that want to transition to I4.0 and better approach the issue. Dhanpat [35] reminds us of the underlying dimensions of I4.0 as a growing need for learning capacities of smart technologies to cope with the new era of cyber-physical systems. Ahmadi et al. [36] addressed the main architecture models of value-chain structure in Industry 4.0.
Industry 4.0 brings both enormous opportunities and challenges for the industry and international trade. It helps not only to modernize the production process and self-initiated execution but also allow the managers to undertake the management of the production process across the globe by creating a flexible global supply chain.
The fourth industrialization is changing the way we perform different kinds of business activities by drawing its main components and their contribution to the business environment. Industry 4.0 is the implementation of cyber-physical systems for creating smart factories by using the IoT, big data, cloud computing, artificial intelligence (AI), and communication technologies for information communication in real-time between the man-machine and machine to machine communication which is redefining the global value chain.
According to Horvàth et al. [37], there are five key drivers of Industry 4.0: Digitalization, optimization, and customization of the production, automation, and adaptation, human and machines interactions, and collaborations, high value-added offers, and automatic exchanges of data and communication. The fourth industrialization has contributed to critical transformation to the international business environment in the different stages of an organization such as human resources, financial systems, management, organizational structure, or production processes.
Those key drivers are highly illustrated by the implementation of cyber-physical systems, the internet of things, smart factories, smart technologies, cloud computing, and big data. The latest architecture of industrialization pursues new objectives and faces completely different challenges that increase in a global perspective. Industry 4.0 offers an opportunity of restructuring declining manufacturing industry in the high-cost-country (HCC) and permit to maintain a strong industrial base in developed countries [38]. It could represent a great opportunity in the context of declining manufacturing in the developed markets. Industry 4.0 answers three key challenges: better competitiveness, flexibility, and agility by facing global offer end demand fluctuation and the regionalization of production [38]. To sum up, Industry 4.0 can be understood as multiple solutions built to change the international industrial sector to gain stronger competitive positions, market shares, especially within a risky business environment. This ambition should be realized by using smart technologies and factories that ensure efficient response to the variation of the global market by improving competitiveness and agile management, which will conduct the changes implied by Industry 4.0.
Central to the fourth industrial revolution is an interconnected network. The internet enables many small firms to participate in global trade, thus, leading to more inclusion. It makes it possible for more products to be exported to more markets, often by newer and younger firms. A 10-percent increase in internet use in the exporting country is found to increase the number of products traded between two countries by 0.4 percent. A similar increase in internet use of a country pair increases the average bilateral trade value per product by 0.6 percent [39]. The transformation implied by the fourth industrialization, Industry 4.0, might lead to significant changes in existing business models allowing new ways to create value. These changes are expected to result in the transformation of traditional value chains. Industry 4.0 affects three elements of manufacturing small and medium enterprises (SMEs): value creation, value capture, and value offer [37].
The 4th industrialization will completely change global value chains by transforming its practices and objectives. The purpose is not limited to monetary rewards but includes new trends such as the willingness to gain efficiency, to create and sustain global competitive advantages, finding new ways of producing, generating innovations, stimulating automation and learning, or even increasing customer implications in the production processes.
Several opportunities generated by Industry 4.0 are transforming the current business levels and activities through its drivers. Multiple business models are flourishing in the Industry 4.0 era. One of the fast-emerging models of them is the
Internet of things (IoT) is retained as a pillar of I4.0. This type of technology provides access to the internet by using deep learning technologies. This equipment transforms machines into smart objects that could, for instance, detect wear, control the performance of the production process, plan the capacity or even manage stocks in real-time. Cloud computing allows interconnection between computers and the internet. It can solve many issues such as Big Data storage as well as the costs and capacities linked to this storage.
Cyber-physical systems (CPS) are mechanisms that allow Humans, software, and machines to interact. It implies an aggregate level of networking. The main purposes of this technique are, by creating such virtual interconnection, to exchange key information to make better strategic decisions. It establishes strong links between production processes, machines, and the virtual world, which work and communicate thanks to computation and the internet in real-time cooperatively. The machines and physical systems will be synchronized to software, and it will allow the control and assessment in real-time production efficiency, adjusting it and making the right strategic decisions easily. Also, CPS enhances the integration of autonomous machines and the collaboration between humans and cyber work.
The result of the use of the different drivers (IoT, CPS, Internet of Service, ERP) will lead to the creation of smart factories, which brings all the smart tools and models together in its production model. This integrated system will facilitate the globalization of production and expansion of global supply chain. It is true that some of manufacturing activities might be re-shored but at the same time, the new smart technology will allow firms to reconfigure their production network overlooking the national boundaries and distance. That is the reason why it is still in the pre-paradigmatic stage of Industry 4.0. implications it is a continuous process that conducts the transformation of our current or traditional methodologies to do business and conceive industrial purposes and processes. As a result, the production model of smart factories becomes cost-effective and flexible to market changes and sustainable, which would reflect the highest level of effectiveness feasible to achieve. This newfound technological prowess will modify drivers of global production networks (GPN), reduce the importance of physical distance as well as re-configure the global value chain (GVC). The new global division of labor (NGDL) is likely to emerge and re-distribute the manufacturing activities integrating different hubs from both the developed, emerging, and developing markets.
There are no doubts about the enormous challenges that Industry 4.0 will bring to the current practice of production, consumption, and global value chain (GVC). Firms and policymakers need to take into consideration adequate strategies to better implement the Industry 4.0 systems, re-organize business activities by taking into consideration of new context and take other caution for the long-term growth of the fourth industrial revolution and reap profit from it. We will define and analyze in this section the challenges raised by Industry 4.0, starting with implementation challenges, then the challenges surrounding the management of Human resources, then the risks to data security, then the Big Data challenges, and finally, the challenges concerning the environment.
As we established earlier, the transition to Industry 4.0 brings countless opportunities for businesses to increase their efficiency and development. However, there are many barriers to the implementation of Industry 4.0, the most important lackings are the shortages of skill-sets that are required in the Industry 4.0 phenomenon. There is also a lack of experience and hindsight on the transition, the necessity to remodel the entire organization, and the coordination of data resources. Added to these challenges are the inequality between SMEs and MNCs in terms of resources, focus, and strategies in the transition to Industry 4.0. This section will present the three main difficulties faced by firms integrating Industry 4.0.
The lack of experience is certainly one of the biggest factors that hold back the businesses from transitioning to Industry 4.0. era. Indeed, the transformation of the companies is very costly, and no clear business case is available as a reference for companies. It is very difficult to justify such investments when there is no perspective, no pattern to follow, and no successful case to reproduce. Therefore, most frequently, companies will either fail in their transition (60% rate of failure) or simply lack the necessary courage to follow through the process of radically changing their organization and investing as much time and resources.
To tackle this challenge effectively, some interesting research in the field has started to emerge, building the first tools to approach the transition. According to Bibby et al. [34], firms should begin by assessing the current level of Industry 4.0 maturity in their specific context or supply network. This analysis will help them determine their strengths and weaknesses and focus their improvement on the right area. Few academic research has been done so far in this area, and many research are done by consulting firms. As an example, in order to assess the industry maturity level of firms, two Industry 4.0 assessment models have been developed in 2016 by consulting firms, IMPULS management consulting GmbH (IMPULS) and PWC. While the PWC model helps companies self-assess their level of maturity based on various criteria, the IMPULS model is focused on delivering improvement advice based on the company’s preparation. More of these models are currently developing, showing that the challenge of the lack of experience will likely be overcome with time as Industry 4.0 spreads across the manufacturing world.
The transition to Industry 4.0 from a traditional organization requires the restructuring of the entire organization, as tasks are automated and decision-making processes are programmed. Every firm that will adopt Industry 4.0 system. We will have to create new business models and define a new strategy. Indeed, this transition requires rethinking the whole organization and processes, interconnecting departments, buying new equipment or modernizing the existing one, re-assigning roles to employees, recruiting new operators, and many other disruptions of their current model. These major changes have a great cost for any business on many levels: financially, of course, but also in terms of time. Therefore, firms have to be especially careful when investing in these transitions in order to not fail its implementation of Industry 4.0.
Another challenge of the implementation of Industry 4.0 is how to connect all data efficiently. Industry 4.0 requires the cooperation of all organizational units, from manufacturing, R&D, IT, to sales and finance departments. Sometimes the walls separating these departments are very hard to break, adding to the difficulty of the transition. But the coordination of functions is only part of the issue: Industry 4.0 requires the management of the large quantities of data generated by diverse sources in the company. For example, production data will have to be processed and coordinated along with data from customer information systems. Data Integration is, therefore, a very difficult task, and the firms need to have the necessary talent from data scientists that will be able to process and model this data.
More than 98% of firms in the developed markets are considered as SMEs, and they are increasingly participating in the global value chains and global trades of goods, services, and components. Introducing the new I4.0 paradigm may have varying levels of difficulty depending on the size and available resources of the targeted firms. Starting conditions between Small and Medium Enterprises (SMEs) and larger firms are obviously very different and bring different challenges. According to Matt et al. [43], SMEs need specific strategies to properly implement I4.0 to their business model.
Large companies will usually follow the higher maturity level in the technological domain faster and more easily than SMEs because of the resources. Indeed, they have more money, expertise, and time to invest in this project. As a consequence, I4.0 is spreading more quickly across large companies which are investing and working intensively on introducing and enabling the necessary technologies. SMEs, however, are lagging behind because they lack the financial and human resources to research into the risks and potential of implementing I4.0. These difficulties further enlarge the gap between SMEs and large multinational companies. However, SMEs have an advantage over large companies, which have a much more complex organizational structure and production processes. Therefore, it is much easier to implement the necessary changes to the organization and culture of SMEs.
According to the study made by Glass et al. [44], across 176 SMEs and 71 large enterprises, numerous barriers to Industry 4.0 must be underlined across business processes and models. The most important challenges include, of course, the multiple issues which arise from Industry 4.0 strategy modeling and the growing need for highly skilled workers with specific know-how, particularly oriented in high technologies, smart engineering, automation, and digitalization competencies and expertise, etc.
We can easily understand that, beyond such technical and future-oriented subjects applying to industries, which is already developed in multiple kinds of business corporations, human resources remain a major challenge for the spread of Industry 4.0 concepts, methodologies, models, and tools. For instance, Mubarak and Petraite [45] have raised a fundamental HR component of Industry 4.0 implementation: The concept of digital trust. Digital trust is situated between trust and Industry 4.0 implementation and implies HR issues. We can identify major human resources issues related to Industry 4.0 as the followings:
When digital trust refers to a new working environment where technology and Humans interact for the welfare of a company and to answer the stakeholder’s needs, a danger of this approach would be the growth of technocentric businesses. In fact, in this model, the stakeholders will give more confidence to technologies, artificial intelligence, and automation to run their business activities and corporations rather than human beings. Indeed, The Deloitte reports questioned the preparedness of HR in an era of Industry 4.0 and the global value chain. Among the 32% of firms that are ready to face technological challenges, only 12% are ready to face the challenges emanating from the Industry 4.0 ecosystem [46]. This statistic illustrates the new trends for companies to focus on efficiency with the highest technological implementation rather than hiring people and maintaining their position through retention policies.
The information systems of human resources (ISHR) illustrate the Industry 4.0 impact upon Human resource function. Indeed, the ISHR technologies permit to automate, standardize with the intervention of smart technologies, activities that belong to HR functions as the following ones: Administrative procedures, training, payrolls management, recruitments, talents management, or even career development of employees within a company [47, 48]. The different systems like automation of robotic processes (ARP) and enterprise resource planning (ERP) were conduct to rethink the HR function. Those different tendencies push HR workers to acquire new competencies geared towards smart technologies and which are transforming their workstation, and which are implying news risks. On the one hand, we can identify the complexity of adaptation to the rapid change of HR function but also the risks linked to the security of information systems and the possibility to lose sensitive data to the benefit of the competition. As a reminder, ISHR systems such as the one proposed by the SAP software can contain confidential data such as the wages, the positions, the personal data of each employee, their curriculum vitae, the annual reports, information posted on the different job board and the main partners of the company, etc.
The fourth revolution required a highly-skilled workforce to be implemented, developed, used and maintained. As a result, a wide range of industries needs a certain level of cooperation between machines and workers. If Industry 4.0 implies this tendency, it also underlines the growing trend of Google, Apple, Facebook, Amazon, Microsoft (GAFAM) to conquer traditional industries in which they have the necessary knowledge and capacities to become undisputable competitors in multiple fields [49]. As an example, we can remember the creation of the Google autonomous car, the collaboration between the Volkswagen group with Amazon web services to collect and analyze its industrial data and becoming a major global leader of the automotive industry, and even the collaboration between Apple and General Electric (GE) to create new applications for the internet of things (IoT) platforms that benefit to GE industries purposes thanks to IOS (exploitation system owned by Apple) opportunities. Industry 4.0 increases competition, in traditional industries and markets (but not only), which seems to be overwhelmed regarding the fast spread of the fourth industrial revolution. To overcome these challenges, companies must recruit high skilled workers, implementing continuous reskilling, learning, and training programs in their HR policies [44]. Besides, one of the major HR issues is constituted by the launch of retention practices which will reduce the diffusion of confidential business information and enhance efficiency and profitability by staying competitive at the same time. We can understand that the rise of high skilled workers’ demand would create a danger if it is not associated with HR policies to enhance workforce abilities to work in a new smart and autonomous workplace.
One major issue to face urgently for HR function is the resistance to change. According to Deloitte [50] report, 17% of their interviewees are ready to manage working environments composed of people, robots, and AI interacting together when 60–70% will fail because they do not manage the adaptation to change properly. Also, Dhanpat et al. [35] confirmed this problem. They have shown that some employees can be resistant to change by being afraid of losing their jobs and being replaced by machines. Bonekamp et al. [51] also agree on the fact that the introduction of Industry 4.0 led to the suppression of standardized tasks by smart and autonomous systems. As a consequence, strong pressure is put on HR managers who require highly skilled people, to train employees and manage to dismiss workers for whom their tasks will be replaced by smart technologies to gain efficiency and competitiveness in the global market. In 2016, The World Economic Forum (WEF) already raised awareness by making an announcement before the opening of the Davos forum: around 5 million jobs in 5 years will be suppressed within 5 years in the main global economies [52]. It is necessary for the HR function globally to answer and react to the exponential expectations of the fourth industrial revolution by taking into account its effect on the global workforce demand and its impact on the global economy and competitiveness.
The fourth industrialization reveals new challenges in business activities such as the management of Bigdata and cybersecurity. Multiple obstacles to Industry 4.0 remain redundant: The constraints are numerous because the digitization of the industry poses formidable problems of standardization and cybersecurity [52].
Indeed, through their researches, one of the major challenges implied by this concept in the working environment is the deployment of Big Data, which creates a growing need to provide a legal framework for the protection of personal data and private life. Among the different cyber issues reported in Industry 4.0, the Deloitte report [50] identifies the top 10 cyber threats and their major data protection concerns.
Indeed, if legal restrictions increase to manage big data challenges, the different issues persist. In terms of an international legal framework, the ISO norm ISO/IEC 27001 defines the data security management for sensitive subjects such as financial, intellectual proprietary, employees, or even data entrusted to another company in the context of business activities. This norm is also called “Management systems of Information security” [53]. In addition, the European Union has implemented the General Data Protection Regulation (GDPR) to mitigate different kinds of challenges affiliated with the management of Big Data. GDPR regulations refer to “imposing a legal framework on the processing of personal data” [54].
However, despite the willingness to build an international legal framework to reduce risk related to Big data cybersecurity, there are still a long-ways to go for a proper framework of Industry 4.0. For instance, Deloitte report has shown that one out of four firms is not developing, implementing, or documenting the industrial cybersecurity (ICS) specific policies and procedures, and more than 33% of manufacturers have not performed any cyber risk assessments specifically focused on the ICS operating on their shop floors, resulting in a potentially significant risk to their operations [55].
In terms of internal management, other issues can arise when a company starts using big data analytics in order to grow. The challenges to take into account include the lack of proper understanding of big data, and therefore, proper usage of the latter; data growth issues, or, “what do I do with this much information?” because the collection of such an amount of data must be useful for something. But what, exactly? Another issue is the confusion when selecting a Big Data tool. There is an increasing number of tools available on the market for firms to have reports and data concerning their businesses. However, it is often not very precise and easy when one is not really aware of what is best for them. This last point brings us to another issue which is the lack of professional expertise in the field of Big Data. Indeed, more and more companies are recruiting professionals and experts in the field of data, such as data scientists, engineers, and analysts. These professions are rare, and as the demand and supply rule confirms, it is quite costly for a firm to recruit, though it is a must when expecting to grow, especially in our current globalized market.
Concerning the international strategies of Industry 4.0 applied to firms, we can find key references in terms of Smart Manufacturing architectures: Reference Architecture Model or Industry 4.0 (RAMI 4.0), Smart manufacturing ecosystem (SME), Intelligent manufacturing system architecture (IMSA). In Smart manufacturing, the architecture corresponds to the designing of the arrangement and connectivity of the organizational structure. The Smart manufacturing ecosystem (SME) provides a standard overview of Smart Manufacturing Systems (SMS). It has three dimensions: product, production, and business. It allows information circulation, in order to follow the production of products through its entire life-cycle. It focuses on the entire value chain and the interaction between the three dimensions.
According to a BGC report on Industry 4.0, related to the German manufacturing industry, Industry 4.0 will be used by an increasing number of firms and generate significant productivity gains of this industry sector (90 to 150 billion EUR). The productivity will improve by 15 to 25%. If material costs are considered, productivity upgrades of 5 to 8% are realistic. Individual effect size depends on the specific manufacturing industry. E.g. industrial component manufacturers will see the largest productivity gains (20 to 30%), while automotive manufacturers may assume 10 to 20% [56]. Furthermore, Industry 4.0 will impact the revenue growth of the German industry. Need from manufacturers for improved devices and new data applications, as well as customer demand for a greater range of increasingly customized products, will provide further revenue growth of around 30 billion euros per year, equivalent to around 1% of German GDP.
The BCG study predicts that the growth and productivity increase described above will also positively impact the employment growth of 6% over the next decade. The need for mechanical engineering workers could increase even more – by up to 10 percent over the same period. In the next few years, the automation trend will replace some low-skilled workers in repetitive and monotonous tasks. However, the increasing use of big data analytics will increase the demand for workers with ICT skills. This shift of needed skills transformation is one of the most important challenges of future growth and innovation. Making the mandatory steps to be economically successful in the world of Industry 4.0 will cost manufacturers about 1 to 1.5 percent of their sales in absolute value over the next decade. Finally, it can be concluded that Industry 4.0 will transform the global value chain, labor market, and logistics.
Global trades are going through lots of volatility from geopolitical instability and natural disasters. The current situation requires businesses to develop their strategic goals for growth, risk management, and global supply chain for the short term, mid-term as well as long term. Manufacturing firms need to develop multi-pronged and multi-disciplinary approaches to address challenges facing current and future supply chain disruptions. The use of advanced technologies like artificial intelligence (AI) and Business analytics can be helpful to analyze large-scale data and keep track of supply chain movements in real-time and develop the ability to re-configure the Supply chain on short notice. A firm’s ability to succeed in global markets will depend on the capacity of the industry to adapt to a rapidly changing business landscape.
To sum up, Industry 4.0 seems to have reached heights when it comes to the organization of enterprises at a global level. We described how international organizations could benefit from Industry 4.0 doing international business. We explained how the components of Industry 4.0 had enhanced many aspects of SMEs and MNCs, by analyzing the evolution of the different phases of the historical context to come to such a strong, advanced stage. We, therefore, defined the industry and its key components to explain its contribution to the organization.
Managers need to develop the ability to identify the opportunities and the strengths brought up by this industrial revolution. We took a look into its efficiency features, and opportunities to satisfy the varied demands thanks to capabilities of customization, and the power of the use of Big Data Analytics, as well as the great impact that this evolution has on the environment. Nevertheless, all these benefits do not come without some challenges. Indeed, Industry 4.0 has full of potentialities of innovation and quite complex transformations to simplify and adapt organizations, especially in terms of human resources because robotics and automation will have huge a repercussion on the social aspect. Most especially, developing and emerging countries that participate in the global value chain by offering advantageous manufacturing production locations will face stiff competition between Industry 4.0 based technologies with those of cheap and abundant labor force in those countries. There is no option other than up-grading the workforce and integrating into the 4.0 era to face these new challenges in the era of Industry 4.0. Finally, as valuable as Big Data can be for the industry, we have found out that it is still a domain that requires particular attention since its use remains quite laborious.
Nonetheless, this modern revolutionary phase is not the last of its category. In fact, the very recent rise of Industry 5.0, a solution provider for people and the planet has flipped the script. Indeed, the new revolution of Industry 5.0 puts an emphasis on the well-being of the workers and captures all the added-value components of Industry 4.0 with the aim of prosperity in the new industry as an ambition for a better future.
Botulinum neurotoxins (BoNTs) are bacterial products and large molecules which are usually embedded into even larger complex proteins (CPs) [1, 2, 3, 4]. In clinical practice, BoNTs have to be applied by injection. This causes activation of local dendritic cells, elicits hit-shock proteins, and leads to local inflammation. Therefore, the induction of antibodies (ABs) can hardly be avoided [5]. The analysis of lymphocytes in BoNT/A or BoNT/B long-term treated patients with movement disorders indicates that in most of these patients, T-cells have responded to the BoNT application [6].
Induced antibodies target epitopes of CPs and BoNT. Some of the ABs do not influence the biological activity of BoNTs, and others reduce or neutralize BoNT action [7]. Neutralizing antibodies (NABs) in immune-resistant patients target epitopes of the heavy [8] or the light chain [9] of the BoNT molecule.
In clinical practice, the relevant question arises whether a partial or complete secondary treatment failure (pSTF or cSTF) results from NAB induction.
For the determination of the presence of NABs, clinical as well as laboratory tests can be used (for a recent discussion, see [10]). Regardless of which test is addressed, little is known about the test-retest liability or variability of repeated measurements of a single serum or serial measurements within a single patient. Nevertheless, the precise determination of the prevalence of ABs heavily depends on the quality (sensitivity and specificity) of NAB testing.
Furthermore, by definition of prevalence, it is necessary to test all members of a cohort if the prevalence of a certain feature in a special cohort has to be determined. Thus, precise determination of the prevalence of neutralizing antibodies in a cohort of BoNT-treated patients implies that a cross-sectional NAB study has to be performed in this cohort.
In the majority of studies reporting on the prevalence of NABs, no cross-sectional testing has been performed. Instead, antibody rates or antibody frequencies (= number of NAB-positive patients/number of patients in the cohort) are determined resulting from NAB testing of selected patients. This procedure crossly underestimates the presence of NABs (comp. [11]).
In their meta-analysis of NABs in BoNT therapy, Fabbri et al. report on an overall NAB frequency of 3.5% in clinically responding patients. In responding patients with spasticity, only 0.7% were reported to be NAB-positive, in patients with dystonia 6.5%. These data are at clear variance with cross-sectional studies reporting 31 positive patients among 212 responding patients with cervical dystonia who were tested by means of the mouse hemidiaphragma assay (MHDA) (= 14.6%; [12]) and 14.3% MHDA-positive patients in long-term treated patients with spasticity [13].
An even more challenging problem is the determination of the temporal development of NAB prevalence. Antibody rates or antibody frequencies do not give any information on the temporal development of NABs, since this ratio between NAB-positive patients and all members of the cohort does not take into account the duration of BoNT treatment.
To analyze the temporal development of NAB formation, the Kaplan-Meier survival analysis has to be performed, calculating the prevalence of NAB-positive patients among those patients with a given duration of treatment. This approach demonstrates that up to 50% of the patients will become NAB-positive when treatment durations exceed 25 years or higher doses are used. In Figure 1, the probability to remain AB-negative is plotted against the duration of treatment in 595 patients. The prevalence of NABs was 82 out of 594 patients (= 13.8%) in the entire cohort, 7 out of 186 patients (= 3.8%) being treated with doses <500 uDU, 49 out of 312 patients (= 15.7%) being treated with doses between 500 and 1000 uDu, and 26 out of 96 patients (= 27%) when doses larger than 1000 uDU were used. To compare doses of different BoNT/A preparations and to determine unified dose units (uDU), aboBoNT/A doses were left unchanged and ona- and incoBoNT/A doses were multiplied by 3. These conversion ratios have been used by Fabbri et al. 2016 [11] and have been discussed by Contarino et al. [14]. The Kaplan-Meier analysis clearly reveals that there is a nonlinear decline of the probability to remain MHDA-negative with the duration of treatment, especially in the higher dose groups.
Kaplan-Meier survival curve to remain AB-negative in patients with cervical dystonia being treated with BoNT/A. With increasing duration of treatment beyond 10 years, the probability to remain AB-negative declines rapidly down to values around 50%.
In summary, induction of NABs occurs frequently and inevitably progresses with the duration of treatment as long as complex protein-containing BoNT/A preparations are used. The induction of NABs is probably significantly lower in complex protein-free BoNT/A preparations [5, 15] (see Section 3 below).
The determination of incidence and prevalence of secondary treatment failure (STF) is even more complex. So far, there is no clear definition of STF. If no response to a BoNT injection can be detected neither by the patient nor the treating physician, the diagnosis of a complete treatment failure (cSTF) is comparably easy [16]. However, this is the end stage of a longer process, starting with an increasing reduction of the duration of action of a BoNT injection before the 4-week peak effect becomes reduced. This has been described in 2004 by Dressler in detail [1].
When patients are reinjected every 3 months, the reduction of the duration of action cannot be measured directly but results in a systematic worsening of disease severity (for details see [5, 17]). We, therefore, have proposed a formal definition of pSTF in patients with CD. If a patient has responded with more than three points on the TSUI scale [18] and then develops a systematic worsening over three injection cycles of more than two TSUI score points and reports a reduction of the effect of BoNT injection to head position, tremor, or pain, a pSTF has to be suspected.
Our experience is that such a formal definition of pSTF is helpful to detect patients with pSTF. Furthermore, in a cohort of 32 patients with pSTF according to this definition, 25 patients (= 78%) had a positive MHDA test [4]. This is definitely more than in a large cohort of patients with suspected pSTF without formal definition were only about 50% were MHDA-positive [19].
This led to the opinion that NAB-associated secondary nonresponse (SnR) is a rare occurrence, and SnR is more frequently due to an insufficient dose, inappropriate muscle selection, or improper injection technique or targeting [10, 20]. But to our opinion, these aspects of BoNT treatment do not suggest the development of pSTF but indicate insufficient and inappropriate BoNT treatment. pSTF can only be suspected when the patient worsens despite of therapy optimization.
In a cross-sectional study on 66 patients with CD who had started their BoNT therapy with abo- or onaBoNT/A, we have analyzed patients´ drawing of the course of disease (course of disease graphs (CoDGs)) after the onset of BoNT therapy over the entire duration of BoNT therapy. Five different response types could be distinguished: the rapid or golden responder (RR) type, the continuous response (CR) type, the poor response (PR) type, and the secondary treatment failure (STF) type I and II.
The RR type is characterized by a rapid response after the onset of BoNT therapy, followed by a further less rapid improvement. The CR type is characterized by a continuous improvement over the entire duration of treatment, The PR type is characterized by an improvement of less than 20%. Patients who drew a PR type CoD graph were primary nonresponders. The STF types I and II are characterized by an initial improvement followed by a secondary worsening. In the STF type II, the second period of improvement followed after the switch of the BoNT preparation.
Among the 66 patients, 17 patients (= 25.8%) produced a STF type. In Figure 2A, the mean CoD graph (full line) plus/minus 1 standard deviation (hatched lines of the 11 patients with a STF type I CoD graph is presented. In Figure 2B, the corresponding mean CoD graph (full line) plus/minus 1 standard deviation of the six STF-type II CoD graphs are presented.
The severity of cervical dystonia versus percentage of time elapsed from treatment onset. A. Mean course of disease graph (CoD graph; solid line) plus 1 standard deviation range (hatched lines) of 11 CD patients who had drawn a STF type I CoD graph after the onset of BoNT therapy. The severity of CD rapidly decreases initially but then worsens again. B. Mean course of disease graph (CoD graph; solid line) plus 1 standard deviation range (hatched lines) of six CD patients who had drawn a STF type II CoD graph after the onset of BoNT therapy. The severity of CD improved initially, then worsened again, but improved a second time after the switch of the BoNT preparation.
Time to paralysis versus TSUI. A. Temporal development of the relation between TSUI scores and paralysis times in 2010, 2013, and 2017 in nine CD patients in whom the complex protein-containing preparation had not been switched, although the initial MHDA test was positive (paralysis time > 60 mins). Open circles indicate values of the investigation in 2010, full circles indicate values of the investigation in 2017, and no circles indicate values of the investigation in 2013. B. Temporal development of the relation between TSUI scores and paralysis times in 2010, 2013, and 2017 in nine CD patients in whom the complex protein-containing preparation was switched to incoBoNT/A in 2010. Open squares indicate values of the investigation in 2010, full squares indicate values of the investigation in 2017, and no squares indicate values of the investigation in 2013. Apart from one exceptional case, paralysis times of eight patients decrease between 2010 and 2017. In six out of nine patients, TSUI scores improve, but the improvement of the TSUI score is less pronounced compared to the improvement of the paralysis times.
The same task (to draw the course of disease after the onset of BoNT therapy) was analyzed in 34 patients who had exclusively been treated with incoBoNT/A. No patient in the incoBoNT/A monotherapy group produced a STF type I or II CoD graph. This difference in frequency of drawing STF type I or II graphs is significant (
In summary, partial secondary treatment failure (pSTF) occurs more frequently than positive NAB tests suggest. This indicates that NAB tests are less sensitive to detect pSTF than careful clinical investigation and patient’s assessment of the efficacy of BoNT therapy.
As mentioned, earlier, the presence of NABs does not imply that there is no clinical response at all. We have recently described a small cohort of nine CD patients with positive NAB testing in 2010 who did not want to be switched to another BoNT preparation. They were retested in 2013 and 2017. Their relation between TSUI scores and paralysis times in 2010, 2013, and 2017 are presented in Figure 3A (open symbols indicate data from 2010, full symbols indicate data from 2017, and missing symbols indicate data from 2013). Apart from two exceptional cases, little changes in paralysis times and TSUI scores can be observed.
The data of these nine CD patients in whom BoNT/A preparation had not been switched between 2010 and 2017 were compared to data of nine CD patients in whom the complex protein-containing BoNT/A preparation was switched to the complex protein-free incoBoNT/A preparation in 2010. The relation between TSUI scores and paralysis times of these nine switchers is presented in Figure 3B. Apart from one exceptional case, paralysis times improved in the switchers. In parallel, the TSUI scores also improved in six out of nine patients, but the improvement of TSUI scores was less pronounced than the improvement of the paralysis times (see Figure 3B).
In summary, so far little is known about the development of NAB titers when patients remain on their BoNT preparation under which they have developed NABs. However, there is increasing evidence that switching from a complex protein-containing preparation (abo- and onaBoNT) to a complex protein-free preparation (incoBoNT/A) may lead to a significant long-lasting improvement of paralysis times [4, 21].
Soon after the treatment of patients with the old “Botox,” it became obvious that in a large percentage of patients, NABs were induced [22]. This led to a purification process of the “old” Botox® preparation, a reduction of the protein load of the “new” Botox® by a factor of 5–6 [10, 23], and an improvement of the antigenicity of the Botox® preparation [24]. The incidence of NAB induction reported for the “new” Botox® preparation was around 1%/year [24].
In 2005, incoBoNT was licensed for the treatment of CD [25]. By removal of botulinum neurotoxin complex proteins and elimination of biological inactive fragments of the BoNT molecule, the protein load of this preparation was reduced down to 0.55 ng compared to 4.8 ng of the Botox and 5.3 ng of the Dysport® preparation [3, 26]. But so far, no convincing study has been presented that the lower protein load of the incoBoNT preparation also leads to a significantly lower antigenicity compared to the other two BoNT/A preparations licensed in Europe.
However, it has not been reported that NABs or pSTF were induced in a patient who had exclusively been treated with incoBoNT/A [15]. Cases with NABs have been presented who had been treated only for a few treatment cycles with abo- or onaBoNT and then were switched to incoBoNT/A [1, 15], but NAB induction under incoBoNT/A monotherapy has not been observed.
This is in line with a recent observation that in 34 CD patients who were exclusively been treated with incoBoNT/A, no patient had a positive MHDA test [15] and no patient drew a STF type I or II CoD graph (see Section 2 above).
In summary, the antigenicity of the complex protein-free incoBoNT/A preparation appears to be very low, since no NAB induction has been observed in patients who have exclusively been treated with incoBoNT/A.
It has been demonstrated that long-term treated CD patients with NABs have a significantly worse TSUI score, were treated with significantly higher doses, and have higher pain scores of the CDQ24 than long-term treated CD patients with a negative MHDA [12, 27, 28]. The paralysis times of the MHDA are significantly correlated with the actual doses, the actual TSUI scores, and the CDQ24 pain scores [28].
To analyze which treatment-related parameter may be used to predict the presence of NABs best, NABs were determined in 59 patients with pSTF. Patients ‘assessments of the effect of long-term BoNT/A treatment were determined by asking patients to estimate the improvement of CD in percent of the initial severity of CD at the onset of BoNT therapy (IMPQ) and to mark the actual severity of CD in percent of the initial severity on a visual analog scale which yielded a second estimation of improvement (IMPD). The receiver operating characteristics (ROC) curves for the prediction of the presence of NABs by IMPQ and IMPD are presented in Figure 4A. The sensitivity and specificity of both parameters were around 0.7–0.8.
The ROC curves for prediction of the presence of NABs by IMPQ and IMPD. A. ROC curves analyzing the relation between the presence of NABs and patients´ assessments of the improvement of CD since the onset of BoNT therapy: Solid circles indicate the ROC curve of IMPQ and light circles indicate the ROC curve of IMPD. For both parameters, sensitivity and specificity lie around 0.7–0.8. B. ROC curves analyzing the relation between the presence of NABs and treating physicians’ scoring of the actual severity of CD (ATSUI) and the improvement of CD since the onset of BoNT therapy (IMPTSUI): Solid squares indicate the ROC curve of ATSUI and light circles indicate the ROC curve of IMPTSUI. For both parameters, the sensitivity is around 0.5, whereas the specificity lies around 0.7–0.8.
The treating physicians scored the actual severity of CD by means of the TSUI score (ATSUI) and determined the improvement since the onset of BoNT therapy by calculating the difference between ATSUI and the initial severity of CD at the onset of BoNT therapy (IMPTSUI) in the same 59 patients. Similar ROC curves were calculated for ATSUI and IMPTSUI (Figure 4B). Treating physicians´ scoring predicted the presence of antibodies less well compared to the assessment of the patients. Sensitivity was lower than 0.6, and specificity was also between 0.7 and 0.8.
In summary, patients realize the NAB-induced reduction of the efficacy of BoNT injections quite well, probably better than treating physicians scoring of the treatment effect.
Induction of NABs occurs frequently (Figure 1), may become manifest after years of successful treatment (Figure 3), progresses with the duration of treatment (Figure 1), and has clinical implications. In patients with CD, it goes along with higher severity of CD, leads to more pain, and affords treatment with increasingly higher doses. Patients realize the reduction of efficacy of BoNT/A treatment quite well (Figure 4).
Since the induction of NABs has not been observed under monotherapy with incoBoNT/A and switch to incoBoNT/A may lead to clinical improvement in patients with pSTF after ona- and aboBoNT/A incoBoNT/A seems to have a very low antigenicity. We, therefore, recommend using the complex protein-free BoNT/A preparation incoBoNT/A from the very beginning of BoNT/A therapy to reduce the risk of antibody formation as low as possible.
We would like to thank the following individuals for their expertise and assistance throughout all aspects of our studies especially Prof. Dr. Philipp Albrecht for making substantial conceptual and design contributions, Dr. Marek Moll, Beyza Ürer, Raphaela Brauns, and Dietmar Rosenthal for contributing to gathering data conducting the data analysis and creating the tables and figures.
The authors declare no conflict of interest.
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Since the protein aggregation process in humans is a slow process, early determination of the patients that will develop neurodegenerative diseases later in life is critical in terms of starting effective treatment, which will reduce the expensive health care. In this chapter, I will discuss the nature of protein aggregation of signature proteins and the status of protein proteolytic systems such as proteasome and autophagosome in Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, frontotemporal lobar degeneration, Huntington’s disease, and prion disease under the light of recent studies including our new findings.",book:{id:"7480",slug:"neurochemical-basis-of-brain-function-and-dysfunction",title:"Neurochemical Basis of Brain Function and Dysfunction",fullTitle:"Neurochemical Basis of Brain Function and Dysfunction"},signatures:"Abdulbaki Agbas",authors:[{id:"250609",title:"Prof.",name:"Abdulbaki",middleName:null,surname:"Agbas",slug:"abdulbaki-agbas",fullName:"Abdulbaki Agbas"}]},{id:"62431",doi:"10.5772/intechopen.79266",title:"The United Chemicals of Cannabis: Beneficial Effects of Cannabis Phytochemicals on the Brain and Cognition",slug:"the-united-chemicals-of-cannabis-beneficial-effects-of-cannabis-phytochemicals-on-the-brain-and-cogn",totalDownloads:1818,totalCrossrefCites:3,totalDimensionsCites:11,abstract:"‘Medicinal cannabis’ can be defined as pharmaceutical grade cannabis-based products used for the treatment of illness. Beneficial treatment effects of cannabidiol (CBD), a major non-intoxicating compound isolated from the cannabis plant, have been shown in multiple states of cognitive impairment, including neurodegenerative (Alzheimer’s, Huntington’s and Parkinson’s disease), neuroinflammatory (sepsis-induced encephalopathy) and neurological disorders (ischemic brain injury). CBD can also treat some of the symptoms of schizophrenia, including cognitive deficits (impairments in learning and memory), which is a major symptom domain of the illness that is largely resistant to existing antipsychotic medications. However, empirical evidence suggests the presence of an ‘entourage effect’ in cannabis; that is, observations that medicinal cannabis seems to work better in some instances when administered as a whole-plant extract. While scientific evidence highlights isolated CBD as a strong candidate for treating cognitive impairment, the entourage effect suggests that the co-operation of other plant molecules could provide further benefits. This chapter explores the scientific evidence surrounding the benefits of CBD and other specific key phytochemicals in cannabis: linalool, α-pinene, β-caryophyllene, flavonoids and anthocyanin, on brain health and cognition.",book:{id:"7040",slug:"recent-advances-in-cannabinoid-research",title:"Recent Advances in Cannabinoid Research",fullTitle:"Recent Advances in Cannabinoid Research"},signatures:"Katrina Weston-Green",authors:null},{id:"55884",doi:"10.5772/intechopen.69111",title:"Production and Function of Serotonin in Cardiac Cells",slug:"production-and-function-of-serotonin-in-cardiac-cells",totalDownloads:1568,totalCrossrefCites:4,totalDimensionsCites:10,abstract:"Serotonin [5-hydroxy-tryptamine (5-HT)] exerts a number of effects in the mammalian heart: increase in heart rate, increase in force of contraction, fibrosis of cardiac valves, coronary constriction, arrhythmias and thrombosis. These effects are, in part, mediated by 5-HT-receptors, in part, directly by 5-HT action on intracellular proteins. In the beginning, 5-HT was thought to be only produced in the gut and then transported into the heart via platelets, because platelets can take up 5-HT in the gut and enter the capillaries and thus the mammalian heart. 5-HT is to a large extent metabolized in the liver and excreted via the urine. Here, we will also overview data that argue for additional pathways, namely production and degradation of 5-HT in the cells of the heart itself.",book:{id:"5780",slug:"serotonin-a-chemical-messenger-between-all-types-of-living-cells",title:"Serotonin",fullTitle:"Serotonin - A Chemical Messenger Between All Types of Living Cells"},signatures:"Joachim Neumann, Britt Hofmann and Ulrich Gergs",authors:[{id:"198376",title:"Prof.",name:"Joachim",middleName:null,surname:"Neumann",slug:"joachim-neumann",fullName:"Joachim Neumann"},{id:"205353",title:"Dr.",name:"Britt",middleName:null,surname:"Hofmann",slug:"britt-hofmann",fullName:"Britt Hofmann"},{id:"205354",title:"Dr.",name:"Ulrich",middleName:null,surname:"Gergs",slug:"ulrich-gergs",fullName:"Ulrich Gergs"}]}],mostDownloadedChaptersLast30Days:[{id:"62431",title:"The United Chemicals of Cannabis: Beneficial Effects of Cannabis Phytochemicals on the Brain and Cognition",slug:"the-united-chemicals-of-cannabis-beneficial-effects-of-cannabis-phytochemicals-on-the-brain-and-cogn",totalDownloads:1813,totalCrossrefCites:3,totalDimensionsCites:11,abstract:"‘Medicinal cannabis’ can be defined as pharmaceutical grade cannabis-based products used for the treatment of illness. Beneficial treatment effects of cannabidiol (CBD), a major non-intoxicating compound isolated from the cannabis plant, have been shown in multiple states of cognitive impairment, including neurodegenerative (Alzheimer’s, Huntington’s and Parkinson’s disease), neuroinflammatory (sepsis-induced encephalopathy) and neurological disorders (ischemic brain injury). CBD can also treat some of the symptoms of schizophrenia, including cognitive deficits (impairments in learning and memory), which is a major symptom domain of the illness that is largely resistant to existing antipsychotic medications. However, empirical evidence suggests the presence of an ‘entourage effect’ in cannabis; that is, observations that medicinal cannabis seems to work better in some instances when administered as a whole-plant extract. While scientific evidence highlights isolated CBD as a strong candidate for treating cognitive impairment, the entourage effect suggests that the co-operation of other plant molecules could provide further benefits. This chapter explores the scientific evidence surrounding the benefits of CBD and other specific key phytochemicals in cannabis: linalool, α-pinene, β-caryophyllene, flavonoids and anthocyanin, on brain health and cognition.",book:{id:"7040",slug:"recent-advances-in-cannabinoid-research",title:"Recent Advances in Cannabinoid Research",fullTitle:"Recent Advances in Cannabinoid Research"},signatures:"Katrina Weston-Green",authors:null},{id:"68776",title:"Introductory Chapter: The Chemical Basis of Neural Function and Dysfunction",slug:"introductory-chapter-the-chemical-basis-of-neural-function-and-dysfunction",totalDownloads:1110,totalCrossrefCites:1,totalDimensionsCites:2,abstract:null,book:{id:"7480",slug:"neurochemical-basis-of-brain-function-and-dysfunction",title:"Neurochemical Basis of Brain Function and Dysfunction",fullTitle:"Neurochemical Basis of Brain Function and Dysfunction"},signatures:"Thomas Heinbockel and Antonei B. Csoka",authors:[{id:"70569",title:"Dr.",name:"Thomas",middleName:null,surname:"Heinbockel",slug:"thomas-heinbockel",fullName:"Thomas Heinbockel"},{id:"245650",title:"Dr.",name:"Antonei B.",middleName:null,surname:"Csoka",slug:"antonei-b.-csoka",fullName:"Antonei B. Csoka"}]},{id:"68712",title:"Synaptic Transmission and Amino Acid Neurotransmitters",slug:"synaptic-transmission-and-amino-acid-neurotransmitters",totalDownloads:1361,totalCrossrefCites:6,totalDimensionsCites:7,abstract:"Amino acids are the most abundant neurotransmitters in the brain. Neurotransmitters are synthesized and stored in presynaptic terminals, released from terminals upon stimulation with specific receptors on the postsynaptic cells. Chemical and electrical synapses are specialized biological structures found in the nervous system; they connect neurons together and transmit signals across the neurons. The process of synaptic transmission generates or inhibits electrical impulses in a network of neurons for the processing of information. Glutamate is the primary excitatory neurotransmitter in the brain, while GABA is the principal inhibitory neurotransmitter. The balance of glutamatergic and GABAergic tone is crucial to normal neurologic function. Through synaptic transmission, this information is communicated from the presynaptic cell to the postsynaptic cell. Amino acid neurotransmitters primarily glutamic acid, GABA, aspartic acid, and glycine are single amino acid residues released from presynaptic nerve terminals in response to an action potential and cross the synaptic cleft to bind with specific receptor on the postsynaptic membrane. The integral role of amino acid neurotransmitters is important on the normal functioning of the brain. The presynaptic and postsynaptic events in chemical synapses are subject to use dependent and highly regulated as per the changes in synaptic neurotransmitter release and function.",book:{id:"7480",slug:"neurochemical-basis-of-brain-function-and-dysfunction",title:"Neurochemical Basis of Brain Function and Dysfunction",fullTitle:"Neurochemical Basis of Brain Function and Dysfunction"},signatures:"Manorama Patri",authors:[{id:"196763",title:"Dr.",name:"Manorama",middleName:null,surname:"Patri",slug:"manorama-patri",fullName:"Manorama Patri"}]},{id:"46296",title:"Physiological Role of Amyloid Beta in Neural Cells: The Cellular Trophic Activity",slug:"physiological-role-of-amyloid-beta-in-neural-cells-the-cellular-trophic-activity",totalDownloads:5908,totalCrossrefCites:19,totalDimensionsCites:32,abstract:null,book:{id:"3846",slug:"neurochemistry",title:"Neurochemistry",fullTitle:"Neurochemistry"},signatures:"M. del C. Cárdenas-Aguayo, M. del C. Silva-Lucero, M. Cortes-Ortiz,\nB. Jiménez-Ramos, L. Gómez-Virgilio, G. Ramírez-Rodríguez, E. Vera-\nArroyo, R. Fiorentino-Pérez, U. García, J. 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Hatch",authors:[{id:"130802",title:"Dr.",name:"Grant",middleName:null,surname:"Hatch",slug:"grant-hatch",fullName:"Grant Hatch"},{id:"170126",title:"Prof.",name:"Donald",middleName:null,surname:"Miller",slug:"donald-miller",fullName:"Donald Miller"},{id:"170127",title:"Mr.",name:"Michael",middleName:null,surname:"Pogorzelec",slug:"michael-pogorzelec",fullName:"Michael Pogorzelec"},{id:"170128",title:"Ms.",name:"Hieu",middleName:null,surname:"Nguyen",slug:"hieu-nguyen",fullName:"Hieu Nguyen"},{id:"170129",title:"Dr.",name:"Ngoc",middleName:null,surname:"On",slug:"ngoc-on",fullName:"Ngoc On"},{id:"170130",title:"Dr.",name:"Siddhartha",middleName:null,surname:"Dalvi",slug:"siddhartha-dalvi",fullName:"Siddhartha Dalvi"}]}],onlineFirstChaptersFilter:{topicId:"1174",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:89,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:104,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:32,numberOfPublishedChapters:318,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:141,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:133,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:113,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:5,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:15,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}},{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}}]},series:{item:{id:"6",title:"Infectious Diseases",doi:"10.5772/intechopen.71852",issn:"2631-6188",scope:"This series will provide a comprehensive overview of recent research trends in various Infectious Diseases (as per the most recent Baltimore classification). Topics will include general overviews of infections, immunopathology, diagnosis, treatment, epidemiology, etiology, and current clinical recommendations for managing infectious diseases. Ongoing issues, recent advances, and future diagnostic approaches and therapeutic strategies will also be discussed. This book series will focus on various aspects and properties of infectious diseases whose deep understanding is essential for safeguarding the human race from losing resources and economies due to pathogens.",coverUrl:"https://cdn.intechopen.com/series/covers/6.jpg",latestPublicationDate:"June 25th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:13,editor:{id:"131400",title:"Prof.",name:"Alfonso J.",middleName:null,surname:"Rodriguez-Morales",slug:"alfonso-j.-rodriguez-morales",fullName:"Alfonso J. Rodriguez-Morales",profilePictureURL:"https://mts.intechopen.com/storage/users/131400/images/system/131400.png",biography:"Dr. Rodriguez-Morales is an expert in tropical and emerging diseases, particularly zoonotic and vector-borne diseases (especially arboviral diseases). He is the president of the Travel Medicine Committee of the Pan-American Infectious Diseases Association (API), as well as the president of the Colombian Association of Infectious Diseases (ACIN). He is a member of the Committee on Tropical Medicine, Zoonoses, and Travel Medicine of ACIN. He is a vice-president of the Latin American Society for Travel Medicine (SLAMVI) and a Member of the Council of the International Society for Infectious Diseases (ISID). Since 2014, he has been recognized as a Senior Researcher, at the Ministry of Science of Colombia. He is a professor at the Faculty of Medicine of the Fundacion Universitaria Autonoma de las Americas, in Pereira, Risaralda, Colombia. He is an External Professor, Master in Research on Tropical Medicine and International Health, Universitat de Barcelona, Spain. He is also a professor at the Master in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. He is currently the Editor in Chief of the journal Travel Medicine and Infectious Diseases. His Scopus H index is 47 (Google Scholar H index, 68).",institutionString:"Institución Universitaria Visión de las Américas, Colombia",institution:null},editorTwo:null,editorThree:null},subseries:{paginationCount:4,paginationItems:[{id:"3",title:"Bacterial Infectious Diseases",coverUrl:"https://cdn.intechopen.com/series_topics/covers/3.jpg",isOpenForSubmission:!1,editor:null,editorTwo:null,editorThree:null},{id:"4",title:"Fungal Infectious Diseases",coverUrl:"https://cdn.intechopen.com/series_topics/covers/4.jpg",isOpenForSubmission:!0,editor:{id:"174134",title:"Dr.",name:"Yuping",middleName:null,surname:"Ran",slug:"yuping-ran",fullName:"Yuping Ran",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bS9d6QAC/Profile_Picture_1630330675373",biography:"Dr. Yuping Ran, Professor, Department of Dermatology, West China Hospital, Sichuan University, Chengdu, China. Completed the Course Medical Mycology, the Centraalbureau voor Schimmelcultures (CBS), Fungal Biodiversity Centre, Netherlands (2006). International Union of Microbiological Societies (IUMS) Fellow, and International Emerging Infectious Diseases (IEID) Fellow, Centers for Diseases Control and Prevention (CDC), Atlanta, USA. Diploma of Dermatological Scientist, Japanese Society for Investigative Dermatology. Ph.D. of Juntendo University, Japan. Bachelor’s and Master’s degree, Medicine, West China University of Medical Sciences. Chair of Sichuan Medical Association Dermatology Committee. General Secretary of The 19th Annual Meeting of Chinese Society of Dermatology and the Asia Pacific Society for Medical Mycology (2013). In charge of the Annual Medical Mycology Course over 20-years authorized by National Continue Medical Education Committee of China. Member of the board of directors of the Asia-Pacific Society for Medical Mycology (APSMM). Associate editor of Mycopathologia. Vice-chief of the editorial board of Chinses Journal of Mycology, China. Board Member and Chair of Mycology Group of Chinese Society of Dermatology.",institutionString:null,institution:{name:"Sichuan University",institutionURL:null,country:{name:"China"}}},editorTwo:null,editorThree:null},{id:"5",title:"Parasitic Infectious Diseases",coverUrl:"https://cdn.intechopen.com/series_topics/covers/5.jpg",isOpenForSubmission:!0,editor:{id:"67907",title:"Dr.",name:"Amidou",middleName:null,surname:"Samie",slug:"amidou-samie",fullName:"Amidou Samie",profilePictureURL:"https://mts.intechopen.com/storage/users/67907/images/system/67907.jpg",biography:"Dr. Amidou Samie is an Associate Professor of Microbiology at the University of Venda, in South Africa, where he graduated for his PhD in May 2008. He joined the Department of Microbiology the same year and has been giving lectures on topics covering parasitology, immunology, molecular biology and industrial microbiology. He is currently a rated researcher by the National Research Foundation of South Africa at category C2. He has published widely in the field of infectious diseases and has overseen several MSc’s and PhDs. His research activities mostly cover topics on infectious diseases from epidemiology to control. His particular interest lies in the study of intestinal protozoan parasites and opportunistic infections among HIV patients as well as the potential impact of childhood diarrhoea on growth and child development. He also conducts research on water-borne diseases and water quality and is involved in the evaluation of point-of-use water treatment technologies using silver and copper nanoparticles in collaboration with the University of Virginia, USA. He also studies the use of medicinal plants for the control of infectious diseases as well as antimicrobial drug resistance.",institutionString:null,institution:{name:"University of Venda",institutionURL:null,country:{name:"South Africa"}}},editorTwo:null,editorThree:null},{id:"6",title:"Viral Infectious Diseases",coverUrl:"https://cdn.intechopen.com/series_topics/covers/6.jpg",isOpenForSubmission:!0,editor:{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",biography:"Professor Dr. Shailendra K. Saxena is a vice dean and professor at King George's Medical University, Lucknow, India. His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. Dr. Saxena is a fellow of various international societies/academies including the Royal College of Pathologists, United Kingdom; Royal Society of Medicine, London; Royal Society of Biology, United Kingdom; Royal Society of Chemistry, London; and Academy of Translational Medicine Professionals, Austria. He was named a Global Leader in Science by The Scientist. He is also an international opinion leader/expert in vaccination for Japanese encephalitis by IPIC (UK).",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",institutionURL:null,country:{name:"India"}}},editorTwo:null,editorThree:null}]},overviewPageOFChapters:{paginationCount:10,paginationItems:[{id:"82380",title:"Evolution of Parasitism and Pathogenic Adaptations in Certain Medically Important Fungi",doi:"10.5772/intechopen.105206",signatures:"Gokul Shankar Sabesan, Ranjit Singh AJA, Ranjith Mehenderkar and Basanta Kumar Mohanty",slug:"evolution-of-parasitism-and-pathogenic-adaptations-in-certain-medically-important-fungi",totalDownloads:4,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Fungal Infectious Diseases - Annual Volume 2022",coverURL:"https://cdn.intechopen.com/books/images_new/11400.jpg",subseries:{id:"4",title:"Fungal Infectious Diseases"}}},{id:"82367",title:"Spatial Variation and Factors Associated with Unsuppressed HIV Viral Load among Women in an HIV Hyperendemic Area of KwaZulu-Natal, South Africa",doi:"10.5772/intechopen.105547",signatures:"Adenike O. 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He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. Dr. Saxena is a fellow of various international societies/academies including the Royal College of Pathologists, United Kingdom; Royal Society of Medicine, London; Royal Society of Biology, United Kingdom; Royal Society of Chemistry, London; and Academy of Translational Medicine Professionals, Austria. He was named a Global Leader in Science by The Scientist. 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My method of translating this into day to day in clinical practice is non-exhaustible and my habit of exchanging knowledge and expertise with others in those fields is the code and secret of success.",institutionString:null,institution:{name:"Majmaah University",country:{name:"Saudi Arabia"}}},{id:"313277",title:"Dr.",name:"Bartłomiej",middleName:null,surname:"Płaczek",slug:"bartlomiej-placzek",fullName:"Bartłomiej Płaczek",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/313277/images/system/313277.jpg",biography:"Bartłomiej Płaczek, MSc (2002), Ph.D. (2005), Habilitation (2016), is a professor at the University of Silesia, Institute of Computer Science, Poland, and an expert from the National Centre for Research and Development. His research interests include sensor networks, smart sensors, intelligent systems, and image processing with applications in healthcare and medicine. He is the author or co-author of more than seventy papers in peer-reviewed journals and conferences as well as the co-author of several books. He serves as a reviewer for many scientific journals, international conferences, and research foundations. Since 2010, Dr. Placzek has been a reviewer of grants and projects (including EU projects) in the field of information technologies.",institutionString:"University of Silesia",institution:{name:"University of Silesia",country:{name:"Poland"}}},{id:"35000",title:"Prof.",name:"Ulrich H.P",middleName:"H.P.",surname:"Fischer",slug:"ulrich-h.p-fischer",fullName:"Ulrich H.P Fischer",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/35000/images/3052_n.jpg",biography:"Academic and Professional Background\nUlrich H. P. has Diploma and PhD degrees in Physics from the Free University Berlin, Germany. He has been working on research positions in the Heinrich-Hertz-Institute in Germany. Several international research projects has been performed with European partners from France, Netherlands, Norway and the UK. He is currently Professor of Communications Systems at the Harz University of Applied Sciences, Germany.\n\nPublications and Publishing\nHe has edited one book, a special interest book about ‘Optoelectronic Packaging’ (VDE, Berlin, Germany), and has published over 100 papers and is owner of several international patents for WDM over POF key elements.\n\nKey Research and Consulting Interests\nUlrich’s research activity has always been related to Spectroscopy and Optical Communications Technology. Specific current interests include the validation of complex instruments, and the application of VR technology to the development and testing of measurement systems. He has been reviewer for several publications of the Optical Society of America\\'s including Photonics Technology Letters and Applied Optics.\n\nPersonal Interests\nThese include motor cycling in a very relaxed manner and performing martial arts.",institutionString:null,institution:{name:"Charité",country:{name:"Germany"}}},{id:"341622",title:"Ph.D.",name:"Eduardo",middleName:null,surname:"Rojas Alvarez",slug:"eduardo-rojas-alvarez",fullName:"Eduardo Rojas Alvarez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/341622/images/15892_n.jpg",biography:null,institutionString:null,institution:{name:"University of Cuenca",country:{name:"Ecuador"}}},{id:"215610",title:"Prof.",name:"Muhammad",middleName:null,surname:"Sarfraz",slug:"muhammad-sarfraz",fullName:"Muhammad Sarfraz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/215610/images/system/215610.jpeg",biography:"Muhammad Sarfraz is a professor in the Department of Information Science, Kuwait University. His research interests include computer graphics, computer vision, image processing, machine learning, pattern recognition, soft computing, data science, intelligent systems, information technology, and information systems. Prof. Sarfraz has been a keynote/invited speaker on various platforms around the globe. He has advised various students for their MSc and Ph.D. theses. He has published more than 400 publications as books, journal articles, and conference papers. He is a member of various professional societies and a chair and member of the International Advisory Committees and Organizing Committees of various international conferences. Prof. Sarfraz is also an editor-in-chief and editor of various international journals.",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"32650",title:"Prof.",name:"Lukas",middleName:"Willem",surname:"Snyman",slug:"lukas-snyman",fullName:"Lukas Snyman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/32650/images/4136_n.jpg",biography:"Lukas Willem Snyman received his basic education at primary and high schools in South Africa, Eastern Cape. He enrolled at today's Nelson Metropolitan University and graduated from this university with a BSc in Physics and Mathematics, B.Sc Honors in Physics, MSc in Semiconductor Physics, and a Ph.D. in Semiconductor Physics in 1987. After his studies, he chose an academic career and devoted his energy to the teaching of physics to first, second, and third-year students. After positions as a lecturer at the University of Port Elizabeth, he accepted a position as Associate Professor at the University of Pretoria, South Africa.\r\n\r\nIn 1992, he motivates the concept of 'television and computer-based education” as means to reach large student numbers with only the best of teaching expertise and publishes an article on the concept in the SA Journal of Higher Education of 1993 (and later in 2003). The University of Pretoria subsequently approved a series of test projects on the concept with outreach to Mamelodi and Eerste Rust in 1993. In 1994, the University established a 'Unit for Telematic Education ' as a support section for multiple faculties at the University of Pretoria. In subsequent years, the concept of 'telematic education” subsequently becomes well established in academic circles in South Africa, grew in popularity, and is adopted by many universities and colleges throughout South Africa as a medium of enhancing education and training, as a method to reaching out to far out communities, and as a means to enhance study from the home environment.\r\n\r\nProfessor Snyman in subsequent years pursued research in semiconductor physics, semiconductor devices, microelectronics, and optoelectronics.\r\n\r\nIn 2000 he joined the TUT as a full professor. Here served for a period as head of the Department of Electronic Engineering. Here he makes contributions to solar energy development, microwave and optoelectronic device development, silicon photonics, as well as contributions to new mobile telecommunication systems and network planning in SA.\r\n\r\nCurrently, he teaches electronics and telecommunications at the TUT to audiences ranging from first-year students to Ph.D. level.\r\n\r\nFor his research in the field of 'Silicon Photonics” since 1990, he has published (as author and co-author) about thirty internationally reviewed articles in scientific journals, contributed to more than forty international conferences, about 25 South African provisional patents (as inventor and co-inventor), 8 PCT international patent applications until now. Of these, two USA patents applications, two European Patents, two Korean patents, and ten SA patents have been granted. A further 4 USA patents, 5 European patents, 3 Korean patents, 3 Chinese patents, and 3 Japanese patents are currently under consideration.\r\n\r\nRecently he has also published an extensive scholarly chapter in an internet open access book on 'Integrating Microphotonic Systems and MOEMS into standard Silicon CMOS Integrated circuitry”.\r\n\r\nFurthermore, Professor Snyman recently steered a new initiative at the TUT by introducing a 'Laboratory for Innovative Electronic Systems ' at the Department of Electrical Engineering. The model of this laboratory or center is to primarily combine outputs as achieved by high-level research with lower-level system development and entrepreneurship in a technical university environment. Students are allocated to projects at different levels with PhDs and Master students allocated to the generation of new knowledge and new technologies, while students at the diploma and Baccalaureus level are allocated to electronic systems development with a direct and a near application for application in industry or the commercial and public sectors in South Africa.\r\n\r\nProfessor Snyman received the WIRSAM Award of 1983 and the WIRSAM Award in 1985 in South Africa for best research papers by a young scientist at two international conferences on electron microscopy in South Africa. He subsequently received the SA Microelectronics Award for the best dissertation emanating from studies executed at a South African university in the field of Physics and Microelectronics in South Africa in 1987. In October of 2011, Professor Snyman received the prestigious Institutional Award for 'Innovator of the Year” for 2010 at the Tshwane University of Technology, South Africa. This award was based on the number of patents recognized and granted by local and international institutions as well as for his contributions concerning innovation at the TUT.",institutionString:null,institution:{name:"University of South Africa",country:{name:"South Africa"}}},{id:"317279",title:"Mr.",name:"Ali",middleName:"Usama",surname:"Syed",slug:"ali-syed",fullName:"Ali Syed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/317279/images/16024_n.png",biography:"A creative, talented, and innovative young professional who is dedicated, well organized, and capable research fellow with two years of experience in graduate-level research, published in engineering journals and book, with related expertise in Bio-robotics, equally passionate about the aesthetics of the mechanical and electronic system, obtained expertise in the use of MS Office, MATLAB, SolidWorks, LabVIEW, Proteus, Fusion 360, having a grasp on python, C++ and assembly language, possess proven ability in acquiring research grants, previous appointments with social and educational societies with experience in administration, current affiliations with IEEE and Web of Science, a confident presenter at conferences and teacher in classrooms, able to explain complex information to audiences of all levels.",institutionString:null,institution:{name:"Air University",country:{name:"Pakistan"}}},{id:"75526",title:"Ph.D.",name:"Zihni Onur",middleName:null,surname:"Uygun",slug:"zihni-onur-uygun",fullName:"Zihni Onur Uygun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/75526/images/12_n.jpg",biography:"My undergraduate education and my Master of Science educations at Ege University and at Çanakkale Onsekiz Mart University have given me a firm foundation in Biochemistry, Analytical Chemistry, Biosensors, Bioelectronics, Physical Chemistry and Medicine. After obtaining my degree as a MSc in analytical chemistry, I started working as a research assistant in Ege University Medical Faculty in 2014. In parallel, I enrolled to the MSc program at the Department of Medical Biochemistry at Ege University to gain deeper knowledge on medical and biochemical sciences as well as clinical chemistry in 2014. In my PhD I deeply researched on biosensors and bioelectronics and finished in 2020. Now I have eleven SCI-Expanded Index published papers, 6 international book chapters, referee assignments for different SCIE journals, one international patent pending, several international awards, projects and bursaries. In parallel to my research assistant position at Ege University Medical Faculty, Department of Medical Biochemistry, in April 2016, I also founded a Start-Up Company (Denosens Biotechnology LTD) by the support of The Scientific and Technological Research Council of Turkey. Currently, I am also working as a CEO in Denosens Biotechnology. The main purposes of the company, which carries out R&D as a research center, are to develop new generation biosensors and sensors for both point-of-care diagnostics; such as glucose, lactate, cholesterol and cancer biomarker detections. My specific experimental and instrumental skills are Biochemistry, Biosensor, Analytical Chemistry, Electrochemistry, Mobile phone based point-of-care diagnostic device, POCTs and Patient interface designs, HPLC, Tandem Mass Spectrometry, Spectrophotometry, ELISA.",institutionString:null,institution:{name:"Ege University",country:{name:"Turkey"}}},{id:"267434",title:"Dr.",name:"Rohit",middleName:null,surname:"Raja",slug:"rohit-raja",fullName:"Rohit Raja",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/267434/images/system/267434.jpg",biography:"Dr. Rohit Raja received Ph.D. in Computer Science and Engineering from Dr. CVRAMAN University in 2016. His main research interest includes Face recognition and Identification, Digital Image Processing, Signal Processing, and Networking. Presently he is working as Associate Professor in IT Department, Guru Ghasidas Vishwavidyalaya (A Central University), Bilaspur (CG), India. He has authored several Journal and Conference Papers. He has good Academics & Research experience in various areas of CSE and IT. He has filed and successfully published 27 Patents. He has received many time invitations to be a Guest at IEEE Conferences. He has published 100 research papers in various International/National Journals (including IEEE, Springer, etc.) and Proceedings of the reputed International/ National Conferences (including Springer and IEEE). He has been nominated to the board of editors/reviewers of many peer-reviewed and refereed Journals (including IEEE, Springer).",institutionString:"Guru Ghasidas Vishwavidyalaya",institution:{name:"Guru Ghasidas Vishwavidyalaya",country:{name:"India"}}},{id:"246502",title:"Dr.",name:"Jaya T.",middleName:"T",surname:"Varkey",slug:"jaya-t.-varkey",fullName:"Jaya T. Varkey",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/246502/images/11160_n.jpg",biography:"Jaya T. Varkey, PhD, graduated with a degree in Chemistry from Cochin University of Science and Technology, Kerala, India. She obtained a PhD in Chemistry from the School of Chemical Sciences, Mahatma Gandhi University, Kerala, India, and completed a post-doctoral fellowship at the University of Minnesota, USA. She is a research guide at Mahatma Gandhi University and Associate Professor in Chemistry, St. Teresa’s College, Kochi, Kerala, India.\nDr. Varkey received a National Young Scientist award from the Indian Science Congress (1995), a UGC Research award (2016–2018), an Indian National Science Academy (INSA) Visiting Scientist award (2018–2019), and a Best Innovative Faculty award from the All India Association for Christian Higher Education (AIACHE) (2019). She Hashas received the Sr. Mary Cecil prize for best research paper three times. She was also awarded a start-up to develop a tea bag water filter. \nDr. Varkey has published two international books and twenty-seven international journal publications. She is an editorial board member for five international journals.",institutionString:"St. Teresa’s College",institution:null},{id:"250668",title:"Dr.",name:"Ali",middleName:null,surname:"Nabipour Chakoli",slug:"ali-nabipour-chakoli",fullName:"Ali Nabipour Chakoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/250668/images/system/250668.jpg",biography:"Academic Qualification:\r\n•\tPhD in Materials Physics and Chemistry, From: Sep. 2006, to: Sep. 2010, School of Materials Science and Engineering, Harbin Institute of Technology, Thesis: Structure and Shape Memory Effect of Functionalized MWCNTs/poly (L-lactide-co-ε-caprolactone) Nanocomposites. Supervisor: Prof. Wei Cai,\r\n•\tM.Sc in Applied Physics, From: 1996, to: 1998, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Determination of Boron in Micro alloy Steels with solid state nuclear track detectors by neutron induced auto radiography, Supervisors: Dr. M. Hosseini Ashrafi and Dr. A. Hosseini.\r\n•\tB.Sc. in Applied Physics, From: 1991, to: 1996, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Design of shielding for Am-Be neutron sources for In Vivo neutron activation analysis, Supervisor: Dr. M. Hosseini Ashrafi.\r\n\r\nResearch Experiences:\r\n1.\tNanomaterials, Carbon Nanotubes, Graphene: Synthesis, Functionalization and Characterization,\r\n2.\tMWCNTs/Polymer Composites: Fabrication and Characterization, \r\n3.\tShape Memory Polymers, Biodegradable Polymers, ORC, Collagen,\r\n4.\tMaterials Analysis and Characterizations: TEM, SEM, XPS, FT-IR, Raman, DSC, DMA, TGA, XRD, GPC, Fluoroscopy, \r\n5.\tInteraction of Radiation with Mater, Nuclear Safety and Security, NDT(RT),\r\n6.\tRadiation Detectors, Calibration (SSDL),\r\n7.\tCompleted IAEA e-learning Courses:\r\nNuclear Security (15 Modules),\r\nNuclear Safety:\r\nTSA 2: Regulatory Protection in Occupational Exposure,\r\nTips & Tricks: Radiation Protection in Radiography,\r\nSafety and Quality in Radiotherapy,\r\nCourse on Sealed Radioactive Sources,\r\nCourse on Fundamentals of Environmental Remediation,\r\nCourse on Planning for Environmental Remediation,\r\nKnowledge Management Orientation Course,\r\nFood Irradiation - Technology, Applications and Good Practices,\r\nEmployment:\r\nFrom 2010 to now: Academic staff, Nuclear Science and Technology Research Institute, Kargar Shomali, Tehran, Iran, P.O. Box: 14395-836.\r\nFrom 1997 to 2006: Expert of Materials Analysis and Characterization. Research Center of Agriculture and Medicine. Rajaeeshahr, Karaj, Iran, P. O. Box: 31585-498.",institutionString:"Atomic Energy Organization of Iran",institution:{name:"Atomic Energy Organization of Iran",country:{name:"Iran"}}},{id:"248279",title:"Dr.",name:"Monika",middleName:"Elzbieta",surname:"Machoy",slug:"monika-machoy",fullName:"Monika Machoy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248279/images/system/248279.jpeg",biography:"Monika Elżbieta Machoy, MD, graduated with distinction from the Faculty of Medicine and Dentistry at the Pomeranian Medical University in 2009, defended her PhD thesis with summa cum laude in 2016 and is currently employed as a researcher at the Department of Orthodontics of the Pomeranian Medical University. She expanded her professional knowledge during a one-year scholarship program at the Ernst Moritz Arndt University in Greifswald, Germany and during a three-year internship at the Technical University in Dresden, Germany. She has been a speaker at numerous orthodontic conferences, among others, American Association of Orthodontics, European Orthodontic Symposium and numerous conferences of the Polish Orthodontic Society. She conducts research focusing on the effect of orthodontic treatment on dental and periodontal tissues and the causes of pain in orthodontic patients.",institutionString:"Pomeranian Medical University",institution:{name:"Pomeranian Medical University",country:{name:"Poland"}}},{id:"252743",title:"Prof.",name:"Aswini",middleName:"Kumar",surname:"Kar",slug:"aswini-kar",fullName:"Aswini Kar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252743/images/10381_n.jpg",biography:"uploaded in cv",institutionString:null,institution:{name:"KIIT University",country:{name:"India"}}},{id:"204256",title:"Dr.",name:"Anil",middleName:"Kumar",surname:"Kumar Sahu",slug:"anil-kumar-sahu",fullName:"Anil Kumar Sahu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204256/images/14201_n.jpg",biography:"I have nearly 11 years of research and teaching experience. I have done my master degree from University Institute of Pharmacy, Pt. Ravi Shankar Shukla University, Raipur, Chhattisgarh India. I have published 16 review and research articles in international and national journals and published 4 chapters in IntechOpen, the world’s leading publisher of Open access books. I have presented many papers at national and international conferences. I have received research award from Indian Drug Manufacturers Association in year 2015. My research interest extends from novel lymphatic drug delivery systems, oral delivery system for herbal bioactive to formulation optimization.",institutionString:null,institution:{name:"Chhattisgarh Swami Vivekanand Technical University",country:{name:"India"}}},{id:"253468",title:"Dr.",name:"Mariusz",middleName:null,surname:"Marzec",slug:"mariusz-marzec",fullName:"Mariusz Marzec",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/253468/images/system/253468.png",biography:"An assistant professor at Department of Biomedical Computer Systems, at Institute of Computer Science, Silesian University in Katowice. Scientific interests: computer analysis and processing of images, biomedical images, databases and programming languages. He is an author and co-author of scientific publications covering analysis and processing of biomedical images and development of database systems.",institutionString:"University of Silesia",institution:null},{id:"212432",title:"Prof.",name:"Hadi",middleName:null,surname:"Mohammadi",slug:"hadi-mohammadi",fullName:"Hadi Mohammadi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/212432/images/system/212432.jpeg",biography:"Dr. Hadi Mohammadi is a biomedical engineer with hands-on experience in the design and development of many engineering structures and medical devices through various projects that he has been involved in over the past twenty years. Dr. Mohammadi received his BSc. and MSc. degrees in Mechanical Engineering from Sharif University of Technology, Tehran, Iran, and his PhD. degree in Biomedical Engineering (biomaterials) from the University of Western Ontario. He was a postdoctoral trainee for almost four years at University of Calgary and Harvard Medical School. He is an industry innovator having created the technology to produce lifelike synthetic platforms that can be used for the simulation of almost all cardiovascular reconstructive surgeries. He’s been heavily involved in the design and development of cardiovascular devices and technology for the past 10 years. He is currently an Assistant Professor with the University of British Colombia, Canada.",institutionString:"University of British Columbia",institution:{name:"University of British Columbia",country:{name:"Canada"}}},{id:"254463",title:"Prof.",name:"Haisheng",middleName:null,surname:"Yang",slug:"haisheng-yang",fullName:"Haisheng Yang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/254463/images/system/254463.jpeg",biography:"Haisheng Yang, Ph.D., Professor and Director of the Department of Biomedical Engineering, College of Life Science and Bioengineering, Beijing University of Technology. He received his Ph.D. degree in Mechanics/Biomechanics from Harbin Institute of Technology (jointly with University of California, Berkeley). Afterwards, he worked as a Postdoctoral Research Associate in the Purdue Musculoskeletal Biology and Mechanics Lab at the Department of Basic Medical Sciences, Purdue University, USA. He also conducted research in the Research Centre of Shriners Hospitals for Children-Canada at McGill University, Canada. Dr. Yang has over 10 years research experience in orthopaedic biomechanics and mechanobiology of bone adaptation and regeneration. He earned an award from Beijing Overseas Talents Aggregation program in 2017 and serves as Beijing Distinguished Professor.",institutionString:null,institution:{name:"Beijing University of Technology",country:{name:"China"}}},{id:"89721",title:"Dr.",name:"Mehmet",middleName:"Cuneyt",surname:"Ozmen",slug:"mehmet-ozmen",fullName:"Mehmet Ozmen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/89721/images/7289_n.jpg",biography:null,institutionString:null,institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"242893",title:"Ph.D. Student",name:"Joaquim",middleName:null,surname:"De Moura",slug:"joaquim-de-moura",fullName:"Joaquim De Moura",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/242893/images/7133_n.jpg",biography:"Joaquim de Moura received his degree in Computer Engineering in 2014 from the University of A Coruña (Spain). In 2016, he received his M.Sc degree in Computer Engineering from the same university. He is currently pursuing his Ph.D degree in Computer Science in a collaborative project between ophthalmology centers in Galicia and the University of A Coruña. His research interests include computer vision, machine learning algorithms and analysis and medical imaging processing of various kinds.",institutionString:null,institution:{name:"University of A Coruña",country:{name:"Spain"}}},{id:"294334",title:"B.Sc.",name:"Marc",middleName:null,surname:"Bruggeman",slug:"marc-bruggeman",fullName:"Marc Bruggeman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/294334/images/8242_n.jpg",biography:"Chemical engineer graduate, with a passion for material science and specific interest in polymers - their near infinite applications intrigue me. \n\nI plan to continue my scientific career in the field of polymeric biomaterials as I am fascinated by intelligent, bioactive and biomimetic materials for use in both consumer and medical applications.",institutionString:null,institution:null},{id:"255757",title:"Dr.",name:"Igor",middleName:"Victorovich",surname:"Lakhno",slug:"igor-lakhno",fullName:"Igor Lakhno",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255757/images/system/255757.jpg",biography:"Igor Victorovich Lakhno was born in 1971 in Kharkiv (Ukraine). \nMD – 1994, Kharkiv National Medical Univesity.\nOb&Gyn; – 1997, master courses in Kharkiv Medical Academy of Postgraduate Education.\nPh.D. – 1999, Kharkiv National Medical Univesity.\nDSC – 2019, PL Shupik National Academy of Postgraduate Education \nProfessor – 2021, Department of Obstetrics and Gynecology of VN Karazin Kharkiv National University\nHead of Department – 2021, Department of Perinatology, Obstetrics and gynecology of Kharkiv Medical Academy of Postgraduate Education\nIgor Lakhno has been graduated from international training courses on reproductive medicine and family planning held at Debrecen University (Hungary) in 1997. Since 1998 Lakhno Igor has worked as an associate professor in the department of obstetrics and gynecology of VN Karazin National University and an associate professor of the perinatology, obstetrics, and gynecology department of Kharkiv Medical Academy of Postgraduate Education. Since June 2019 he’s been a professor in the department of obstetrics and gynecology of VN Karazin National University and a professor of the perinatology, obstetrics, and gynecology department. He’s affiliated with Kharkiv Medical Academy of Postgraduate Education as a Head of Department from November 2021. Igor Lakhno has participated in several international projects on fetal non-invasive electrocardiography (with Dr. J. A. Behar (Technion), Prof. D. Hoyer (Jena University), and José Alejandro Díaz Méndez (National Institute of Astrophysics, Optics, and Electronics, Mexico). He’s an author of about 200 printed works and there are 31 of them in Scopus or Web of Science databases. Igor Lakhno is a member of the Editorial Board of Reproductive Health of Woman, Emergency Medicine, and Technology Transfer Innovative Solutions in Medicine (Estonia). He is a medical Editor of “Z turbotoyu pro zhinku”. Igor Lakhno is a reviewer of the Journal of Obstetrics and Gynaecology (Taylor and Francis), British Journal of Obstetrics and Gynecology (Wiley), Informatics in Medicine Unlocked (Elsevier), The Journal of Obstetrics and Gynecology Research (Wiley), Endocrine, Metabolic & Immune Disorders-Drug Targets (Bentham Open), The Open Biomedical Engineering Journal (Bentham Open), etc. He’s defended a dissertation for a DSc degree “Pre-eclampsia: prediction, prevention, and treatment”. Three years ago Igor Lakhno has participated in a training course on innovative technologies in medical education at Lublin Medical University (Poland). Lakhno Igor has participated as a speaker in several international conferences and congresses (International Conference on Biological Oscillations April 10th-14th 2016, Lancaster, UK, The 9th conference of the European Study Group on Cardiovascular Oscillations). His main scientific interests: are obstetrics, women’s health, fetal medicine, and cardiovascular medicine. \nIgor Lakhno is a consultant at Kharkiv municipal perinatal center. He’s graduated from training courses on endoscopy in gynecology. He has 28 years of practical experience in the field.",institutionString:null,institution:null},{id:"244950",title:"Dr.",name:"Salvatore",middleName:null,surname:"Di Lauro",slug:"salvatore-di-lauro",fullName:"Salvatore Di Lauro",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0030O00002bSF1HQAW/ProfilePicture%202021-12-20%2014%3A54%3A14.482",biography:"Name:\n\tSALVATORE DI LAURO\nAddress:\n\tHospital Clínico Universitario Valladolid\nAvda Ramón y Cajal 3\n47005, Valladolid\nSpain\nPhone number: \nFax\nE-mail:\n\t+34 983420000 ext 292\n+34 983420084\nsadilauro@live.it\nDate and place of Birth:\nID Number\nMedical Licence \nLanguages\t09-05-1985. Villaricca (Italy)\n\nY1281863H\n474707061\nItalian (native language)\nSpanish (read, written, spoken)\nEnglish (read, written, spoken)\nPortuguese (read, spoken)\nFrench (read)\n\t\t\nCurrent position (title and company)\tDate (Year)\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. Private practise.\t2017-today\n\n2019-today\n\t\n\t\nEducation (High school, university and postgraduate training > 3 months)\tDate (Year)\nDegree in Medicine and Surgery. University of Neaples 'Federico II”\nResident in Opthalmology. Hospital Clinico Universitario Valladolid\nMaster in Vitreo-Retina. IOBA. University of Valladolid\nFellow of the European Board of Ophthalmology. Paris\nMaster in Research in Ophthalmology. University of Valladolid\t2003-2009\n2012-2016\n2016-2017\n2016\n2012-2013\n\t\nEmployments (company and positions)\tDate (Year)\nResident in Ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl.\nFellow in Vitreo-Retina. IOBA. University of Valladolid\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. \n\t2012-2016\n2016-2017\n2017-today\n\n2019-Today\n\n\n\t\nClinical Research Experience (tasks and role)\tDate (Year)\nAssociated investigator\n\n' FIS PI20/00740: DESARROLLO DE UNA CALCULADORA DE RIESGO DE\nAPARICION DE RETINOPATIA DIABETICA BASADA EN TECNICAS DE IMAGEN MULTIMODAL EN PACIENTES DIABETICOS TIPO 1. Grant by: Ministerio de Ciencia e Innovacion \n\n' (BIO/VA23/14) Estudio clínico multicéntrico y prospectivo para validar dos\nbiomarcadores ubicados en los genes p53 y MDM2 en la predicción de los resultados funcionales de la cirugía del desprendimiento de retina regmatógeno. Grant by: Gerencia Regional de Salud de la Junta de Castilla y León.\n' Estudio multicéntrico, aleatorizado, con enmascaramiento doble, en 2 grupos\nparalelos y de 52 semanas de duración para comparar la eficacia, seguridad e inmunogenicidad de SOK583A1 respecto a Eylea® en pacientes con degeneración macular neovascular asociada a la edad' (CSOK583A12301; N.EUDRA: 2019-004838-41; FASE III). Grant by Hexal AG\n\n' Estudio de fase III, aleatorizado, doble ciego, con grupos paralelos, multicéntrico para comparar la eficacia y la seguridad de QL1205 frente a Lucentis® en pacientes con degeneración macular neovascular asociada a la edad. (EUDRACT: 2018-004486-13). Grant by Qilu Pharmaceutical Co\n\n' Estudio NEUTON: Ensayo clinico en fase IV para evaluar la eficacia de aflibercept en pacientes Naive con Edema MacUlar secundario a Oclusion de Vena CenTral de la Retina (OVCR) en regimen de tratamientO iNdividualizado Treat and Extend (TAE)”, (2014-000975-21). Grant by Fundacion Retinaplus\n\n' Evaluación de la seguridad y bioactividad de anillos de tensión capsular en conejo. Proyecto Procusens. Grant by AJL, S.A.\n\n'Estudio epidemiológico, prospectivo, multicéntrico y abierto\\npara valorar la frecuencia de la conjuntivitis adenovírica diagnosticada mediante el test AdenoPlus®\\nTest en pacientes enfermos de conjuntivitis aguda”\\n. National, multicenter study. Grant by: NICOX.\n\nEuropean multicentric trial: 'Evaluation of clinical outcomes following the use of Systane Hydration in patients with dry eye”. Study Phase 4. Grant by: Alcon Labs'\n\nVLPs Injection and Activation in a Rabbit Model of Uveal Melanoma. Grant by Aura Bioscience\n\nUpdating and characterization of a rabbit model of uveal melanoma. Grant by Aura Bioscience\n\nEnsayo clínico en fase IV para evaluar las variantes genéticas de la vía del VEGF como biomarcadores de eficacia del tratamiento con aflibercept en pacientes con degeneración macular asociada a la edad (DMAE) neovascular. Estudio BIOIMAGE. IMO-AFLI-2013-01\n\nEstudio In-Eye:Ensayo clínico en fase IV, abierto, aleatorizado, de 2 brazos,\nmulticçentrico y de 12 meses de duración, para evaluar la eficacia y seguridad de un régimen de PRN flexible individualizado de 'esperar y extender' versus un régimen PRN según criterios de estabilización mediante evaluaciones mensuales de inyecciones intravítreas de ranibizumab 0,5 mg en pacientes naive con neovascularización coriodea secunaria a la degeneración macular relacionada con la edad. CP: CRFB002AES03T\n\nTREND: Estudio Fase IIIb multicéntrico, randomizado, de 12 meses de\nseguimiento con evaluador de la agudeza visual enmascarado, para evaluar la eficacia y la seguridad de ranibizumab 0.5mg en un régimen de tratar y extender comparado con un régimen mensual, en pacientes con degeneración macular neovascular asociada a la edad. CP: CRFB002A2411 Código Eudra CT:\n2013-002626-23\n\n\n\nPublications\t\n\n2021\n\n\n\n\n2015\n\n\n\n\n2021\n\n\n\n\n\n2021\n\n\n\n\n2015\n\n\n\n\n2015\n\n\n2014\n\n\n\n\n2015-16\n\n\n\n2015\n\n\n2014\n\n\n2014\n\n\n\n\n2014\n\n\n\n\n\n\n\n2014\n\nJose Carlos Pastor; Jimena Rojas; Salvador Pastor-Idoate; Salvatore Di Lauro; Lucia Gonzalez-Buendia; Santiago Delgado-Tirado. Proliferative vitreoretinopathy: A new concept of disease pathogenesis and practical\nconsequences. Progress in Retinal and Eye Research. 51, pp. 125 - 155. 03/2016. DOI: 10.1016/j.preteyeres.2015.07.005\n\n\nLabrador-Velandia S; Alonso-Alonso ML; Di Lauro S; García-Gutierrez MT; Srivastava GK; Pastor JC; Fernandez-Bueno I. Mesenchymal stem cells provide paracrine neuroprotective resources that delay degeneration of co-cultured organotypic neuroretinal cultures.Experimental Eye Research. 185, 17/05/2019. DOI: 10.1016/j.exer.2019.05.011\n\nSalvatore Di Lauro; Maria Teresa Garcia Gutierrez; Ivan Fernandez Bueno. Quantification of pigment epithelium-derived factor (PEDF) in an ex vivo coculture of retinal pigment epithelium cells and neuroretina.\nJournal of Allbiosolution. 2019. ISSN 2605-3535\n\nSonia Labrador Velandia; Salvatore Di Lauro; Alonso-Alonso ML; Tabera Bartolomé S; Srivastava GK; Pastor JC; Fernandez-Bueno I. Biocompatibility of intravitreal injection of human mesenchymal stem cells in immunocompetent rabbits. Graefe's archive for clinical and experimental ophthalmology. 256 - 1, pp. 125 - 134. 01/2018. DOI: 10.1007/s00417-017-3842-3\n\n\nSalvatore Di Lauro, David Rodriguez-Crespo, Manuel J Gayoso, Maria T Garcia-Gutierrez, J Carlos Pastor, Girish K Srivastava, Ivan Fernandez-Bueno. A novel coculture model of porcine central neuroretina explants and retinal pigment epithelium cells. Molecular Vision. 2016 - 22, pp. 243 - 253. 01/2016.\n\nSalvatore Di Lauro. Classifications for Proliferative Vitreoretinopathy ({PVR}): An Analysis of Their Use in Publications over the Last 15 Years. Journal of Ophthalmology. 2016, pp. 1 - 6. 01/2016. DOI: 10.1155/2016/7807596\n\nSalvatore Di Lauro; Rosa Maria Coco; Rosa Maria Sanabria; Enrique Rodriguez de la Rua; Jose Carlos Pastor. Loss of Visual Acuity after Successful Surgery for Macula-On Rhegmatogenous Retinal Detachment in a Prospective Multicentre Study. Journal of Ophthalmology. 2015:821864, 2015. DOI: 10.1155/2015/821864\n\nIvan Fernandez-Bueno; Salvatore Di Lauro; Ivan Alvarez; Jose Carlos Lopez; Maria Teresa Garcia-Gutierrez; Itziar Fernandez; Eva Larra; Jose Carlos Pastor. Safety and Biocompatibility of a New High-Density Polyethylene-Based\nSpherical Integrated Porous Orbital Implant: An Experimental Study in Rabbits. Journal of Ophthalmology. 2015:904096, 2015. DOI: 10.1155/2015/904096\n\nPastor JC; Pastor-Idoate S; Rodríguez-Hernandez I; Rojas J; Fernandez I; Gonzalez-Buendia L; Di Lauro S; Gonzalez-Sarmiento R. Genetics of PVR and RD. Ophthalmologica. 232 - Suppl 1, pp. 28 - 29. 2014\n\nRodriguez-Crespo D; Di Lauro S; Singh AK; Garcia-Gutierrez MT; Garrosa M; Pastor JC; Fernandez-Bueno I; Srivastava GK. Triple-layered mixed co-culture model of RPE cells with neuroretina for evaluating the neuroprotective effects of adipose-MSCs. Cell Tissue Res. 358 - 3, pp. 705 - 716. 2014.\nDOI: 10.1007/s00441-014-1987-5\n\nCarlo De Werra; Salvatore Condurro; Salvatore Tramontano; Mario Perone; Ivana Donzelli; Salvatore Di Lauro; Massimo Di Giuseppe; Rosa Di Micco; Annalisa Pascariello; Antonio Pastore; Giorgio Diamantis; Giuseppe Galloro. Hydatid disease of the liver: thirty years of surgical experience.Chirurgia italiana. 59 - 5, pp. 611 - 636.\n(Italia): 2007. ISSN 0009-4773\n\nChapters in books\n\t\n' Salvador Pastor Idoate; Salvatore Di Lauro; Jose Carlos Pastor Jimeno. PVR: Pathogenesis, Histopathology and Classification. Proliferative Vitreoretinopathy with Small Gauge Vitrectomy. Springer, 2018. ISBN 978-3-319-78445-8\nDOI: 10.1007/978-3-319-78446-5_2. \n\n' Salvatore Di Lauro; Maria Isabel Lopez Galvez. Quistes vítreos en una mujer joven. Problemas diagnósticos en patología retinocoroidea. Sociedad Española de Retina-Vitreo. 2018.\n\n' Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor Jimeno. iOCT in PVR management. OCT Applications in Opthalmology. pp. 1 - 8. INTECH, 2018. DOI: 10.5772/intechopen.78774.\n\n' Rosa Coco Martin; Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor. amponadores, manipuladores y tinciones en la cirugía del traumatismo ocular.Trauma Ocular. Ponencia de la SEO 2018..\n\n' LOPEZ GALVEZ; DI LAURO; CRESPO. OCT angiografia y complicaciones retinianas de la diabetes. PONENCIA SEO 2021, CAPITULO 20. (España): 2021.\n\n' Múltiples desprendimientos neurosensoriales bilaterales en paciente joven. Enfermedades Degenerativas De Retina Y Coroides. SERV 04/2016. \n' González-Buendía L; Di Lauro S; Pastor-Idoate S; Pastor Jimeno JC. Vitreorretinopatía proliferante (VRP) e inflamación: LA INFLAMACIÓN in «INMUNOMODULADORES Y ANTIINFLAMATORIOS: MÁS ALLÁ DE LOS CORTICOIDES. RELACION DE PONENCIAS DE LA SOCIEDAD ESPAÑOLA DE OFTALMOLOGIA. 10/2014.",institutionString:null,institution:null},{id:"265335",title:"Mr.",name:"Stefan",middleName:"Radnev",surname:"Stefanov",slug:"stefan-stefanov",fullName:"Stefan Stefanov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/265335/images/7562_n.jpg",biography:null,institutionString:null,institution:null},{id:"243698",title:"Dr.",name:"Xiaogang",middleName:null,surname:"Wang",slug:"xiaogang-wang",fullName:"Xiaogang Wang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243698/images/system/243698.png",biography:"Dr. Xiaogang Wang, a faculty member of Shanxi Eye Hospital specializing in the treatment of cataract and retinal disease and a tutor for postgraduate students of Shanxi Medical University, worked in the COOL Lab as an international visiting scholar under the supervision of Dr. David Huang and Yali Jia from October 2012 through November 2013. Dr. Wang earned an MD from Shanxi Medical University and a Ph.D. from Shanghai Jiao Tong University. Dr. Wang was awarded two research project grants focused on multimodal optical coherence tomography imaging and deep learning in cataract and retinal disease, from the National Natural Science Foundation of China. 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